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Objective:We aimed to investigate the effect of ambulatory blood pressure (BP) on aortic valve calcification (AVC) and coronary artery calcification (CAC), which are subclinical atherosclerotic diseases., Methods:In this population-based, cross-sectional study, we assessed office BP, mean ambulatory BP (24-h, awake, and asleep), and variability of ambulatory BP, as determined by the coefficient of variation (awake and asleep). AVC and CAC were quantified using an Agatston score (>0) based on computed tomography scanning. We calculated relative risks (RRs) and 95% confidence intervals (CIs) with a 1-standard deviation increment in each BP index for the presence of AVC and CAC using a multivariate-adjusted Poisson regression with robust error variance., Results:Of 483 participants (mean age: 66.8 years), 154 (31.9%) and 310 (64.2%) had AVC and CAC, respectively. The presence of AVC was associated with office systolic BP (SBP; RR, 1.15; 95% CI, 1.03-1.28), awake diastolic BP (DBP) variability (RR, 1.12; 95% CI, 1.01-1.25), and asleep SBP variability (RR, 1.14; 95% CI, 1.03-1.27). The presence of CAC was associated with office SBP (RR, 1.08; 95% CI, 1.01-1.15), mean 24-h SBP (RR, 1.10; 95% CI, 1.04-1.16), mean awake SBP (RR, 1.11; 95% CI, 1.04-1.17), mean asleep SBP (RR, 1.07; 95% CI, 1.01-1.13), and asleep SBP variability (RR, 1.07; 95% CI, 1.01-1.13)., Conclusion:These findings highlight the association of ambulatory BP indices with both AVC and CAC, but with different effects on their presences.

Aims This review aims to provide an update of available methods for imaging calcification activity and potential therapeutic options. Data Synthesis: Aortic valve calcification represents the most common heart valve condition requiring treatment among adults in Western societies. No medical therapies are proven to be effective in treating symptoms or reducing disease progression. Therefore, surgical or transcatheter aortic valve replacement remains the only available treatment option. Elevated circulating concentrations of lipoprotein(a) is strongly associated with degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Conclusions: new therapeutic targets have been identified and new imaging techniques could be used to test the effectiveness of new agents and further clarify the pathophysiology of AVS. No therapy that specifically lowers Lp (a) levels has been approved for clinical use.

Impairment of extracellular and intracellular calcium homeostasis can have a damaging effect on the functioning of both individual organs and systems and the whole organism. In the cardiovascular system, disorders ofcalcium metabolism trigger a cascade of auto-inflammatory responses, leading to persistent morphological and functional disturbances. In this review, impaired calcium homeostasis is defined as a predictor of the development of hypersensitivity in cardiovascular diseases. We analyzed the development of a cardiovascular pathology (atherosclerosis, aortic valve calcification, and essential hypertension) with impaired calcium metabolism and pathological mechanisms that cause the disturbances. Calcium sensors, polymorphic variants of genes, and hormones involved in calcium metabolism can reveal the features of calcium metabolism and contribute to a personalized approach to treatment of cardiovascular diseases.

Aims Aortic valve calcification (AVC) detected by non-contrast computed tomography (NCCT) associates with morbidity and mortality in patients with aortic valve stenosis. However, the importance of AVC in the general population is sparsely evaluated. We intend to describe the associations between AVC score on NCCT and echocardiographic findings as left atrial (LA) dilatation, left ventricular (LV) hypertrophy, aortic valve area (AVA), peak velocity, mean gradient, and aortic valve replacement (AVR) in a population with AVC scores ≥300 AU. Methods and results Of 10 471 males aged 65–74 years from the Danish Cardiovascular Screening trial (DANCAVAS), participants with AVC score ≥300 AU were invited for transthoracic echocardiography and 828 (77%) of 1075 accepted the invitation. AVC scores were categorized (300–599, 600–799, 800–1199, and ≥1200 AU). AVR was obtained from registries. AVC was significantly associated with a steady increase in LA dilation (10.5%, 16.3%, 15.8%, 19.6%, P = 0.031), LV hypertrophy (3.9%, 6.6%, 8.9%, 10.1%, P = 0.021), peak velocity (1.7, 1.9, 2.1, 2.8 m/s, P = 0001), mean gradient (6, 8, 11, 19 mmHg, P = 0.0001), and a decrease in AVA (2.0, 1.9, 1.7, 1.3 cm2, P = 0.0001). The area under the curve was 0.79, 0.93, and 0.92 for AVA ≤1.5 cm2, peak velocity ≥3.0 m/s, and mean gradient ≥20 mmHg, respectively, and the associated optimal AVC score thresholds were 734, 1081, and 1019 AU. AVC > 1200 AU was associated with AVR (P Conclusion Among males from the background population, increasing AVC scores were associated with LA dilatation, LV hypertrophy, AVA, peak aortic velocity, mean aortic gradient, and AVR.

Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.

Background and Aims: Mutations of the NT5E gene encoding the cluster of differentiation 73 (CD73) protein have been found in patients with characteristic calcification of joints and arteries (CALJA). CD73 plays a protective role against aortic valve calcification and its deletion results in aortic valve calcification. However, there have been no reports of a patient with CALJA with aortic stenosis. Methods: We describe two extremely rare cases of two sisters with identical NT5E gene mutation patterns, both of whom presented severe aortic stenosis and limb ischemia. Genetic examination for definitive diagnosis was also performed in both patients. Results: Both patients underwent aortic valve replacement and bilateral distal arterial bypass surgeries successfully. They were genetically diagnosed with CALJA based on the NT5E mutation. Conclusions: NT5E mutation should be considered in patients requiring aortic valve replacement for a calcified aortic valve and bypass surgery for specific calcified and occluded arteries.

ObjectiveAortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60–74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.MethodsParticipants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.Results14 073 men aged 60–74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0–82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.ConclusionsAVC was prevalent in the general population of men aged 60–74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.Trial registration numberNCT03946410 and ISRCTN12157806.

The objective of our study was to determine the relationship between exposure to environmental tobacco smoke (ETS) and the value of the aortic valve calcification score (AVCS) in people suffering from arterial hypertension (AH). 107 non-smokers with AH (mean age 67.16 ± 8.48 years) were qualified for the study. The degree of exposure to ETS was assessed using the Second-hand Smoke Exposure Scale (SHSES) questionnaire. Study group was divided depending on ETS exposure: A—no exposure, B—low, C—medium and D—high. AVCS was measured based on the aortic valve plane multiplanar reconstruction from the non-contrast phase of the cardiac computed tomography. The Agatston algorithm was used, in which calcifications were considered changes with a density exceeding 130 HU. The mean AVCS value in the study group of patients was 213.59 ± 304.86. The AVCS was significantly lower in subgroup A than in subgroups C and D. In subgroup A, the lack of aortic valve calcification (AVCS = 0) was observed significantly more frequently than in subgroups C and D. There was a positive correlation between the number of SHSES points and the AVCS value (r = 0.37, p

Background:Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (μmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL).Methods and Results:A community-based random sample of Japanese men aged 40-79 years examined in 2006-2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23-3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23-3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC., Conclusions:The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.

Objectives Optimizing valve implantation depth (ID) plays a crucial role in minimizing conduction disturbances and achieving optimal functional integrity. Until now, the impact of intraprocedural fast (FP) or rapid ventricular pacing (RP) on the implantation depth has not been investigated. Therefore, we aimed to (1) evaluate the impact of different pacing maneuvers on ID, and (2) identify the independent predictors of deep ID. Methods 473 TAVR patients with newer-generation self-expanding devices were retrospectively enrolled and one-to-one propensity-score-matching was performed, resulting in a matching of 189 FP and RP patients in each cohort. The final ID was analyzed, and the underlying functional, anatomical, and procedural conditions were evaluated by univariate and multivariate analysis. Results The highest ID was reached under RP in severe aortic valve calcification and valve size 26 mm. Multivariate analysis identified left ventricular outflow (LVOT) calcification [OR 0.50 (0.31–0.81) p = 0.005*], a “flare” aortic root [OR 0.42 (0.25–0.71), p = 0.001*], and RP (OR 0.49 [0.30–0.79], p = 0.004*) as independent highly preventable predictors of a deep ID. In a model of protective factors, ID was significantly reduced with the number of protective criteria (0–2 criteria: − 5.7 mm ± 2.6 vs. 3–4 criteria − 4.3 mm ± 2.0; p Conclusion Data from this retrospective analysis indicate that RP is an independent predictor to reach a higher implantation depth using self-expanding devices. Randomized studies should prove for validation compared to fast and non-pacing maneuvers during valve delivery and their impact on implantation depth. Trail registration Clinical Trial registration: NCT01805739. Graphic abstract Study design: Evaluation of the impact of different pacing maneuvers (fast ventricular pacing—FP vs. rapid ventricular pacing—RP) on implantation depth (ID). After one-to-one-propensity-score-matching, independent protective and risk factors for a very deep ID beneath 6 mm toward the LVOT (®. AVC aortic valve calcification.

We investigated aortic valve calcification (AVC) distribution and predictors for leaflet calcification patterns in patients with severe tricuspid aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR). Patients undergoing routine multi-sliced computed tomography (MSCT) for procedural planning were enrolled. MSCT data were transferred to a dedicated workstation for evaluation (3mensio Structural Heart™, Pie Medical Imaging BV, Maastricht, The Netherlands) and analyzed. Participants were separated into asymmetrical (AC) and symmetrical (SC) leaflet calcification and potential predictors for calcification distribution were identified with univariate and multivariate regression analysis. 567 Participants with severe tricuspid AS were divided into asymmetrical (AC, n = 443; 78.1%) and symmetrical (SC, n = 124; 21.9%) AVC. In AC, the non-coronary cusp was the most calcified cusp (n = 238; 57.7%). SC is more common in females (AC/SC: 49.2% vs. 67.7%; p 67° (OR 1.68 [1.00–2.80], p = 0.049) as predictors for SC, although with only moderate predictive value. Data from this retrospective analysis indicate that SC occurs more frequently in females. The cumulative leaflet calcification burden is higher in patients with AC, who also present with larger aortic root dimensions. The predictive value for prominent calcification of different aortic valve cusps in AC patients was only low to moderate. Trial registration number: NCT01805739. Supplementary Information The online version contains supplementary material available at 10.1007/s10554-021-02248-6.

Background: While an association between atherosclerosis and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and cognitive impairment (CI). Objective: We sought to determine whether AVC derived from lung cancer screening CT (LCSCT) was associated with CI in a moderate-to-high atherosclerotic risk cohort. Methods: This was a single site, retrospective analysis of 1401 U.S. veterans (65 years [IQI: 61, 68] years; 97%male) who underwent quantification of AVC from LCSCT indicated for smoking history. The primary outcome was new diagnosis of CI identified by objective testing (Mini-Mental Status Exam or Montreal Cognitive Assessment) or by ICD coding. Time-to-event analysis was carried out using AVC as a continuous variable. Results: Over 5 years, 110 patients (8%) were diagnosed with CI. AVC was associated with new diagnosis of CI using 3 Models for adjustment: 1) age (HR: 1.104; CI: 1.023–1.191; p = 0.011); 2) Model 1 plus hypertension, hyperlipidemia, diabetes, CKD stage 3 or higher (glomerular filtration rate

Background There is conflicting data regarding the association between low levels of plasma vitamin D and ischemic heart disease. We aimed to investigate the relationship between plasma vitamin D levels and heart valve calcification in hospitalized patients with ischemic heart disease versus non-ischemic heart disease controls. Methods A prospective case-control study comprising two age and gender-matched groups. The study group included consecutive patients hospitalized due to acute coronary syndrome; the control group included consecutive non-ischemic heart disease patients hospitalized for noncardiac causes. Blood samples for 25-hydroxyvitamin D level were drawn. An echocardiogram was performed during the first 3 days of hospitalization and reviewed for presence and degree of valvular calcification. Results Forty patients with acute coronary syndrome and 40 controls (age 58 ± 11 years, 64% male in both groups) were included. Mean plasma 25-hydroxyvitamin D vitamin level in the entire cohort was 24.5 ± 8 ng/ml. Valve calcification rates were similar in acute coronary syndrome versus non-acute coronary syndrome group (28 vs. 21 had valvular calcification; 18 vs. 12 had aortic valve calcification; 21 vs. 14 had mitral valve calcification, respectively; P = NS for all). We found no significant relationship between vitamin D level and valvular calcification, aortic valve calcification, or mitral valve calcification rate or degree in the entire cohort and in each group alone (P = NS for all). There was a negative correlation between 25-hydroxyvitamin D levels and age in the acute coronary syndrome group (r = -0.399, P = 0.012). Conclusions We did not find a significant relationship between plasma vitamin D levels and the rate or degree of calcification of either aortic/mitral/both valves in hospitalized patients with or without ischemic heart disease.

BACKGROUND AND AIMS: Calcific aortic valve disease is highly prevalent in patients with significant smoking history and is a marker of atherosclerosis. The aim of this study was to define the prognostic value of aortic valve calcification (AVC) derived from low dose, lung cancer screening computed tomography (LCSCT) for all-cause mortality in this higher risk population. METHODS: This is a single site, retrospective analysis of 1529 moderate-to-high atherosclerotic cardiovascular risk U.S. veterans (65 years [IQI: 61, 68] years; 96% male), who underwent clinically indicated LCSCT. CTs were scored for aortic valve calcification (AVC) and coronary artery calcification (CAC). The primary endpoint was all-cause mortality and secondary endpoints were nonfatal myocardial infarction (MI) and nonfatal cerebrovascular accident (CVA). RESULTS: Over 4-year follow-up, 227 patients (15%) died, 112 patients (7%) had nonfatal MI, and 52 patients (3%) had nonfatal CVA. AVC was predictive of all-cause mortality (HR per 100: 1.041 [1.030–1.052], p < 0.001), and this association remained significant after multivariate adjustment for traditional atherosclerotic risk factors, including CAC (1.021 [1.007–1.036], p = 0.003). After excluding patients with severe aortic stenosis (AS) or severe AVC (≥1274 AU in women and ≥2065 AU in men), in a subset of 765 patients who had echocardiograms, this association remained significant after multivariate analysis (HR per 100: 1.052 [1.010–1.095], p = 0.014). Despite controlling for CAC in the models, AVC was still associated with MI (HR per 100: 1.021 [1.004–1.039], p = 0.017) and with CVA (HR per 100: 1.027 [1.002–1.051], p = 0.032). CONCLUSIONS: Scoring AVC derived from LCSCT is predictive of mortality, nonfatal MI, and nonfatal CVA in patients at known risk for cardiovascular disease, independent of coronary calcification or severe aortic valve stenosis.

Smoking is a major risk factor for both cardiovascular disease (CVD) and lung cancer. Aortic valve calcification (AVC) and coronary artery calcification (CAC) are both due to atherosclerotic disease. We aim to investigate whether AVC on low-dose CT (LDCT) predicts death from CVD in smokers beyond that provided by CAC. We reviewed a prospective cohort of 8618 smokers enrolled in LDCT screening for lung cancer in New York State between June 2000 and December 2005. As of December 2009, 169 of the 643 deaths were due to CVD; median follow-up time was 96.4 months. Visual AVC was assessed as being absent (AVC = 0) or present (AVC > 0). CAC ordinal scores of 0–12 were categorized into three validated prognostic categories (0, 1–3, and 4–12). Cox proportional hazards regression analysis was used to assess whether AVC > 0 increased the risk of CVD death, after adjustment for CAC categories and other risk factors. The prevalence of AVC significantly increased (p 0 and CAC ≥ 4, the hazard ratio was 2.35 (95%CI 1.57–3.50) compared with the reference group of AVC = 0 and CAC 0 and CAC ≥ 4 had more than a 2-fold increased risk of CVD death than the group with AVC = 0 and CAC

Graphical abstract, Highlights • H2S derived from CSE/CBS inhibits inflammation and calcification of valvular interstitial cells. • H2S releasing molecules inhibits inflammation and calcification of valvular interstitial cells. • H2S inhibits inflammation and calcification in aortic valve of apolipoprotein E deficient mice. • H2S suppresses nuclear translocation of NF-κB and subsequent expression of IL-1β and TNF-α. • Activation of Runx2, its nuclear translocation is mediated by NF-κB in calcifying conditions. • Inflammation and calcification are connected via master transcription factors, NF-κB and Runx2., Introduction Hydrogen sulfide (H2S) was revealed to inhibit aortic valve calcification and inflammation was implicated in the pathogenesis of calcific aortic valve disease (CAVD). Objectives We investigate whether H2S inhibits mineralization via abolishing inflammation. Methods and results Expression of pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased in patients with CAVD and in calcified aortic valve of ApoE-/- mice. Administration of H22S releasing donor (4-methoxyphenyl piperidinylphosphinodithioc acid (AP72)) exhibited inhibition on both calcification and inflammation in aortic valve of apolipoprotein E knockout mice (ApoE-/-) mice is reflected by lowering IL-1β and TNF-α levels. Accordingly, AP72 prevented the accumulation of extracellular calcium deposition and decreased nuclear translocation of nuclear factor-κB (NF-κB) in human valvular interstitial cells (VIC). This was also accompanied by reduced cytokine response. Double-silencing of endogenous H2S producing enzymes, Cystathionine gamma-lyase (CSE) and Cystathionine beta-synthase (CBS) in VIC exerted enhanced mineralization and higher levels of IL-1β and TNF-α. Importantly, silencing NF-κB gene or its pharmacological inhibition prevented nuclear translocation of runt-related transcription factor 2 (Runx2) and subsequently the calcification of human VIC. Increased levels of NF-κB and Runx2 and their nuclear accumulation occurred in ApoE-/- mice with a high-fat diet. Administration of AP72 decreased the expression of NF-κB and prevented its nuclear translocation in VIC of ApoE-/- mice on a high-fat diet, and that was accompanied by a lowered pro-inflammatory cytokine level. Similarly, activation of Runx2 did not occur in VIC of ApoE-/- mice treated with H2S donor. Employing Stimulated Emission Depletion (STED) nanoscopy, a strong colocalization of NF-κB and Runx2 was detected during the progression of valvular calcification. Conclusions Hydrogen sulfide inhibits inflammation and calcification of aortic valve. Our study suggests that the regulation of Runx2 by hydrogen sulfide (CSE/CBS) occurs via NF-κB establishing a link between inflammation and mineralization in vascular calcification.

Background Compared to high gradient aortic stenosis (AS), patients with low-flow, low-gradient AS have higher mortality after transcatheter aortic valve replacement (TAVR), but distinct outcome predictors in this patient subset are yet to be determined. The present study investigated the prognostic impact of aortic valve calcification (AVC) in patients with low-flow, low-gradient AS undergoing TAVR. Methods This retrospective single-center analysis includes all patients undergoing TAVR for severe low-flow, low-gradient AS (n = 526), ie, low EF low gradient AS (LEF-LG AS; n = 290) and paradoxical low-flow, low-gradient AS (PLF-LG AS; n = 236), in whom AVC was quantified from contrast-enhanced multislice computed tomography images. AVCdensity was defined as calcium volume per annulus area. Patients were trichotomized according to sex-specific AVCdensity tertiles in both subgroups. All-cause mortality was assessed by Kaplan-Meier analyses and independent outcome predictors were determined by multivariable analyses. Results In both subgroups, patients with high AVCdensity had higher mean transvalvular gradients at baseline and higher rates of PVL after TAVR. High AVCdensity was associated with lowest 1- and 3-year mortality after TAVR in the LEF-LG AS but not in the PLF-LG AS group. According to multivariable analysis AVCdensity was independently associated with better survival in LEF-LG AS patients (HR 0.73 [0.60-0.88], P = .0011), but not in those with PLF-LG AS (HR 0.91 [0.73-1.14], P = .42). Conclusions Quantification of AVC may not only be of diagnostic but also of prognostic value, as it facilitates the selection of LEF-LG AS patients with higher probability of beneficial outcome after TAVR.

Background: Echocardiography-derived calcium score (ECS) was able to predict the presence of extensive coronary calcium and obstructive Coronary artery disease(CAD), assessed using Multi slice CT (MSCT) coronary angiography. Furthermore, significant linear trends were observed between ECS and extent and severity of coronary atherosclerosis and number of calcified coronary artery lesions. Objective: To correlate an echocardiography-derived calcium score (ECS), obtained using coronary artery calcium Score (CACS) and the presence of obstructive CAD. Patients and Methods: The study comprised 100 patients (males and females) presented with symptoms suspected of stable CAD. All cases were recruited from the outpatient clinic in Agouza police Hospital in Cairo and Islamic center of Al-Azhar University during a period of fourteen months from 1/11/2018 to 30/12/2019. Results: Linear regression analysis identified that the most independent variables that can predict AVC were CAC score, dyslipidemia, and the most independent variable that can predict obstructive coronary artery disease was the presence of coronary artery calcification and higher CAC score. ROC curve analysis was used to test the predictive value of aortic valve calcification (AVC), Mitral annulus calcification (MAC) and CAC scores for the presence or absence of obstructive CAD. This analysis showed that AVC and MAC scores were inferior to CAC score which was found to have the highest predictive value evidenced by an area under the curve of 0.763 (95%CI: 0.781, 0.913). MAC score was inferior to AVC score which was found to have the highest predictive value evidenced by an area under the curve of 0.815 (95%CI: 0.758, 0.879). Conclusion: The echocardiographic calcium scores specifically the MVC and AVC was correlated to be CAC. ECS can predict the CAC score. ECS can predict the presence or absence CAD.

Aims The aims of this study were to investigate the correlation and sex differences between total valve calcium, valve calcium concentration, and aortic valve calcification (AVC) in explanted valves from patients with severe aortic valve stenosis undergoing aortic valve replacement (AVR). Methods and results Sixty-nine patients with severe aortic stenosis (AS) scheduled for elective AVR underwent echocardiography and cardiac computed tomography (CT) prior to surgery (AVCin vivo) and CT of the explanted aortic valve (AVCex vivo). Explanted valves were prepared in acid solution, sonicated, and analysed with Arsenazo III dye to estimate total valve calcium and valve calcium concentration. Median AVCex vivo was 2082 (1421–2973) AU; mean valve calcium concentration was 1.43 ± 0.42 µmol Ca2+/mg tissue; median total valve calcium 156 (111–255) mg Ca2+, and valve calcium density 52 (35–81) mg/cm2. AVC displayed a strong correlation with total valve calcium (R2 = 0.98, P Conclusion AVC score provides a strong estimate for total valve calcium but to a lesser degree calcium concentration in the valve tissue of patients with severe AS. Females presented lower valvular calcium concentrations than males irrespective of AS severity, adding evidence and providing support to the important point that sex differences in valvular calcium concentration in AS does not reflect valvular size.

Aortic valve calcification severity has been associated with higher rates of aortic regurgitation (AR) following TAVR, but scarce data exist on its impact with the use of newer generation transcatheter heart valves.This was a multicenter study including 626 patients with severe aortic stenosis who underwent TAVR with the SAPIEN 3 valve. Patients were divided in 2 groups according to the median index calcium score (iCS) for each sex: high CS (HCS, iCS ≥ median), and low iCS (LCS, iCS median). Another analysis was performed in those patients with extreme iCS (ECS, iCS75th percentile for each sex). Clinical and echocardiographic data were collected prospectively in a dedicated database.The mean CS was 3758 ± 1417 AU and 1616 ± 691 AU in the HCS and LCS groups, respectively (p 0.001). There were no differences between groups in 30-day mortality (HCS:2.6%, LCS:1.0%, p = 0.13) and stroke (HCS:2.6%,LCS:2.6%, p = 1.0) rates, but all cases (n = 5) of annulus rupture occurred in the HCS group (1.6% vs. 0%, p = 0.061). The incidence of moderate-severe AR post-TAVR was low in both groups (HCS:1.6%,LCS:1.6%, p = 1.0), and valve gradient and area were similar between groups. The results remained similar in the ECS group (mean CS:4607 ± 1424 AU), but a mildly increased mean transvalvular gradient post-TAVR was observed in ECS patients (12.1 ± 5.6 vs 11.0 ± 4.3 mmHg; p = 0.015).Aortic valve calcification severity failed to impact mortality/stroke rates following TAVR with the SAPIEN 3 valve. Low rates of significant AR were observed irrespective of CS, and a mild increase in transvalvular gradient was observed in ECS patients.

Purpose Cardiovascular mortality remains high among patients with diabetes compared with the general population. The primary aim was to evaluate the interest in and demand for advanced cardiovascular screening in patients with diabetes; the secondary aim was to explore its efficiency in detecting unprotected subclinical cardiovascular disease (CVD). Patients and methods In a cross-sectional design, randomly selected 40-60-year-old men and women with diabetes were invited to the screening trial. Screening encompassed (1) a comprehensive medical interview; (2) non-contrast computed tomography scanning to quantify coronary artery and aortic valve calcification, to measure left atrial size, to assess heart rhythm and to detect aortic and iliac dilatations; (3) ankle and brachial blood pressure measurements; and (4) blood and urine samples for measurements of HbA1c, lipid profile, renal function, NT-pro B-type natriuretic peptide (pro-BNP) and albuminuria. Primary outcome was participation rate; secondary outcome was rate of unprotected subclinical CVD. Results Of 465 invited patients, 191 (41.1%) attended screening. The participation rate was 40% (95% CI:33-47) for males and 42% (95% CI:36-48) for females. Twenty-four patients were excluded due to previous CVD. The remaining patients' mean age was 52 years; 58% were males. Subclinical CVD was found in 64%, with a male preponderance (males 75% (95% CI:66-83; females 49% (95% CI:37-60)). Presence of severe coronary artery calcification (score ≥ 400) showed a male preponderance (males 19% (95% CI:12-27); females 7% (95% CI:3-16)). Aortic valve calcification, enlarged left atrial volume, atrial fibrillation, aortic dilatations, peripheral artery disease or increased pro-BNP were uncommon, and without any sex differences. Unprotected subclinical CVD was very common, and medical treatment was intensified in 60% (95% CI:53-68) of patients. Conclusion We propose a feasible cardiovascular screening examination from which middle-aged patients with diabetes may benefit. However, the participation rate may be too low to warrant screening.

Aortic valve stenosis (AS) is the third most common cardiovascular disease. The prevalence of both AS and arterial hypertension increases with age, and the conditions therefore often co-exist. Co-existence of AS and arterial hypertension is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Arterial hypertension may also influence grading of AS, leading to underestimation of the true AS severity. Current guidelines suggest re-assessing patients once arterial hypertension is controlled. Management of arterial hypertension in AS has historically been associated with prudence and concerns, mainly related to potential adverse consequences of drug-induced peripheral vasodilatation combined with reduced stroke volume due to the fixed LV outflow obstruction. Current evidence suggests that patients should be treated with antihypertensive drugs blocking the renin–angiotensin–aldosterone system, adding further drug classes when required, to achieve similar target blood pressure (BP) values as in hypertensive patients without AS. The introduction of transcatheter aortic valve implantation has revolutionized the management of patients with AS, but requires proper BP management during and following valve replacement. The purpose of this document is to review the recent evidence and provide practical expert advice on management of hypertension in patients with AS.

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.

Aortic valve calcification leads to the deposition of calcium phosphate minerals in the extracellular matrix of the aortic valve leaflets. The mineral deposits can severely narrow the opening of the aortic valve, leading to aortic stenosis. There are no therapies to halt or slow down disease progression and the mechanisms governing aortic valve calcification are still poorly understood. Recently, several studies have shown that for the same aortic stenosis severity, women present significantly lower calcification loads than men. The cause of this sex-related difference is unknown. To understand this difference, we analyzed mineral deposits from surgically excised calcified human aortic valves with different material characterization techniques. We find profound differences in mineral composition and morphology between sexes, which strongly suggest that minerals form slower in women than in men and follow a different mineralization pathway. This finding paves the way for new approaches specifically geared towards men or women in the diagnosis and treatment of aortic valve calcification. STATEMENT OF SIGNIFICANCE: Aortic valve calcification is a health disorder with increasing prevalence and high morbidity and mortality. Currently there is no approved effective treatment; the only available therapeutic option is invasive valve replacement, to which not all patients are suited. The main reason for such lack of treatment options is our lack of understanding of the calcification mechanism. In this study, we show profound differences in mineral composition and morphology between sexes, suggesting that aortic valve calcification follows different mineralization pathways in men and women. These findings pave the way for new approaches specifically geared towards men or women in the diagnosis and treatment of aortic valve calcification.

International audience; Aortic valve stenosis remains the most frequent structural heart disease, especially in the elderly. During the last decade, we noticed an important consideration and a huge number of publications related to the medical and surgical treatment of this disease. However, the molecular aspect of this degenerative issue has also been more widely studied recently. As evidenced in oncologic but also cardiac research fields, the emergence of microRNAs in the molecular screening and follow-up makes them potential biomarkers in the future, for the diagnosis, follow-up and treatment of aortic stenosis. Herein, we present a review on the implication of microRNAs in the aortic valve disease management. After listing and describing the main miRNAs of interest in the field, we provide an outline to develop miRNAs as innovative biomarkers and innovative therapeutic strategies, and describe a groundbreaking pre-clinical study using inhibitors of miR-34a in a pre-clinical model of aortic valve stenosis.

Prediction of patients at risk of aortic valve stenosis (AS), AS progression rate, and aortic bioprosthesis dysfunction are of major importance for clinical management and/or prevention. Many imaging modalities may be used; however, they may not be conclusive or available for all patients. Circulating biomarkers are easily available and may be related to a disease or process such as aortic valve calcification or associated with a risk factor of the disease. This article reviews current blood biomarkers associated with aortic valve stenosis/calcification and bioprosthesis dysfunction.

Severe aortic stenosis (AS) is associated with a progressive cardiac remodeling that ultimately leads to heart failure and death if the valve is not replaced. The confirmation of AS severity is therefore crucial to adequately manage patients with AS. Transthoracic echocardiography is the first-line examination to confirm AS severity, but it may be inconclusive in discordant cases. In this setting, AS severity should be confirmed using a multimodality imaging approach. This review gives an overview of how to assess and/or confirm AS severity, especially in case of discordance.

60-year-old female with history of 33mm ATS mechanical mitral valve replacement 16 years ago for rheumatic mitral valve disease and permanent Atrial Fibrillation (AF) presented with one-year history of worsening exertional dyspnoea as well as symptom of pre-syncope. She was on warfarin for AF as well as mechanical mitral valve replacement (MVR) with therapeutic anticoagulation in the recent time. Her transthoracic echocardiogram was technically difficult as MVR leaflet motion and aortic valve morphology was not well visualised because of artefact from mechanical mitral valve (Panel 1 A: 4chamber still echo image showing reverberation artefact from mechanical mitral valve leaflets)) and aortic valve calcification. Doppler Echocardiography revealed significant aortic stenosis (AS) and mildly elevated gradients across the MVR with average peak (17 ​mmHg)/mean (6.5 ​mmHg) gradients and Effective Orifice Area (ERO) of 1.9cm2 (normal >2 cm2) at heart rate of 60bpm in AF raising a possibility of only mild mechanical prosthetic mitral valve stenosis.

Background and aimsSex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD). High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women. We now examined the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants.MethodsWe studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels. ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4±0.9 years. We used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately.ResultsThe mean age was 65±9 and 62±10 years for women and men, respectively. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only. In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors.ConclusionsIn this diverse cohort free of CVD, we found some associations of SH with ECC measures. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.

The authors in that article addressed a very important and relevant issue. Background Epicardial adipose tissue (EAT) is a complex endocrine organ that plays an important role in the development of unfavorable metabolic and cardiovascular risk profile. EAT may express a variety of inflammatory mediators which may contribute to the pathogenesis of coronary artery disease (CAD). Aortic and mitral valve calcification may reflect generalized atherosclerosis in the elderly and may be a marker of high prevalence and severity of CAD. There is a direct correlation (extent, severity and the future CV events) between the coronary artery calcium and the CAD. Aim and Objectives To correlate peri-coronary epicardial adipose tissue and coronary artery calcification and valvular (aortic and mitral) calcification with the severity of the coronary artery disease. Patients and Methods The study recruited 200 patients with suspected coronary artery disease. The amount of EAT surrounding the left main and the three main coronary arteries was quantified in axial cuts with the most distinct layer of EAT. The amount of calcium in the aortic and mitral valve and the coronaries were quantified with multi-detector computed tomography MDCT using dedicated software for measuring calcium score that is based on Agatson score. Coronary artery disease severity was assessed in terms of number of vessels affected and the severity of coronary stenosis by multi-planner reformation technique. Results Based on the finding of the MDCT and according to the presence of calcification in the aortic or the mitral valves, and the significance of the coronary artery disease, patients were classified into two groups, group (I): 115 patients with normal coronaries or with non significant lesions in their coronaries, and group (II): 85 patients with significant coronary artery disease. The Mean ± SD (in millimeters) of EAT for the entire study cohort in various coronary artery locations were as follows: LM EAT 9.82 ± 2.67, proximal LAD EAT 10.06 ± 2.80, mid LAD EAT 9.15 ± 2.41, distal LAD EAT 6.46 ± 1.87, proximal LCX EAT 8.10 ± 1.90, distal LCX EAT 6.83 ± 1.79, proximal RCA EAT 10.23 ± 2.42, mid RCA EAT 9.26 ± 2.72, distal RCA EAT 7.25 ± 2.58. Statistically highly significant difference was observed between the two groups with regards to LM EAT, proximal, mid and distal LAD EAT, proximal and distal LCX EAT, proximal, mid and distal RCA EAT (8.38 ± 2.18 Vs 11.77 ± 1.94 P: 0.000, 8.49 ± 2.21 Vs 12.18 ± 2.00, 7.93 ± 1.77 Vs 10.81 ± 2.16, 5.45 ± 1.26 Vs 7.82 ± 1.68 P: 0.000, 7.08 ± 1.34 Vs 9.46 ± 1.67, 6.05 ± 1.50 Vs 7.89 ± 1.61 P: 0.000, 9.01 ± 1.94 Vs 11.88 ± 1.99, 8.07 ± 2.32 Vs 10.86 ± 2.39, 6.31 ± 2.26 Vs 8.51 ± 2.45 P: 0.000; respectively). Statistically highly significant difference was observed between the two groups with regards calcium score and the severity of CAD in the three major vessels (LAD, LCX and RCA) and the total calcium score in all vessels (35 (16 – 85.5) Vs 179.5 (59.5 – 243) P: 0.000, 20.5 (7 – 50.5) Vs 56 (33 – 95) P: 0.000, 31 (9 – 54) Vs 97 (54 – 199) P: 0.000, 12 (0 – 84) Vs 286 (106 – 511) P:0.000; respectively) while calcium score in the LM was not statistically significant with the severity of CAD (4 (3 – 26) Vs 12 (9 – 16) P: 0.360). As regards aortic valve calcification there was statistically highly significant difference between the two groups; P value 0.000, while mitral valve calcification was found to be not statistically significant between the two groups P: 0.272. Conclusion The present study demonstrated a significant correlation between the peri-coronary epicardial adipose tissue, coronary calcification and aortic valve calcification and the severity of the coronary artery disease.

Introduction Chronic inflammation promotes aortic valve calcification. It is known that epicardial fat is a source of inflammation. The aim of this study was to investigate the relationship between epicardial fat thickness, cardiac conduction disorders and outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods During a three-year period, 45 patients with severe aortic stenosis who underwent TAVI were recruited to the study. Data were collected retrospectively. Epicardial fat was defined as the adipose tissue between the epicardium and the visceral pericardium. Mean epicardial fat thickness was determined by multi-slice computed tomography, which was performed before the procedure. Results The average thickness of epicardial fat was 13.06 ± 3.29 mm. This study failed to reveal a significant correlation between epicardial fat thickness and post-procedural left bundle branch block, right bundle branch block, paravalvular aortic regurgitation and pacemaker implantation rates (p > 0.05). Conclusions The results of this study failed to show a significant relationship between epicardial fat thickness, cardiac conduction disorders and outcomes, however further studies with larger sample numbers are required to explore the relationship.

Background Transcatheter aortic valve implantation (TAVI) has proven efficacy in the treatment of aortic stenosis (AS). Understandably, there is increasing enthusiasm for its use to treat aortic regurgitation (AR). However, there are significant anatomical differences between AS and AR which make TAVI for AR more complex. Case summary We present the case of technically challenging TAVI for severe AR, which was complicated by a traumatic ventricular septal defect (VSD) that required percutaneous closure. To our knowledge, this is the first published case of VSD post-TAVI for AR. Discussion This unanticipated complication highlights anatomical differences between TAVI use in AS and AR. Lack of aortic valve calcification and excessive annular compliance made stable deployment of a self-expanding valve extremely challenging. Despite device oversizing, repeated embolization of the prosthesis into the left ventricular outflow tract traumatized the interventricular septum.

Aortic valve calcification (AVC) is central in the pathophysiology and progression of aortic stenosis (AS). Quantification of AVC by using noncontrast multidetector computed tomography (MDCT) via the Agatston method (analogous to coronary calcium scoring) has shown an excellent correlation with

Calcific aortic stenosis (AS) is characterised by an initial inflammatory phase, with endothelial damage, lipoprotein infiltration and oxidative stress. This stage is followed by a disorganisation of the extracellular matrix with an overproduction of collagen fibres and a mineralisation phase in which valvular interstitial cells differentiate into an osteoblast-like cell type, leading to microcalcification analogue to skeletal bone formation. This self-perpetuating cycle of progressive fibrocalcific remodelling leads to macrocalcification, increases valve rigidity and therefore narrows the effective orifice area, increasing left ventricular afterload and ultimately provoking myocardial damage and symptoms (figure 1).1 Valvular fibrosis, although understudied, appears to play a major role in younger, bicuspid valve and female patients and is one of the reasons sex-specific thresholds are used to define severe AS by CT aortic valve calcification (CT-AVC) quantification (2000 Agatston units (AU) for men and 1200 AU for women).2 The pathogenic model depicted in figure 1 is not necessarily followed in a serial fashion, and although the advance of the disease is inexorable, the rate of AS progression remains largely unpredictable. However, some markers of rapid progression have been described, such as systolic hypertension,3 bicuspid morphology4 and metabolic syndrome.5 Figure 1 Model of AS progression. Pathophysiological model of serial AS progression (‘aortic stenosis cascade’, in blue), along with imaging biomarkers targeting each phase (red) and potential disease-modifying treatments being currently tested in randomised clinical trials (green). 1South Korean PCSK9 inhibitors (NCT03051360); 2EAVaLL: early aortic valve lipoprotein(a) lowering (NCT02109614); 3SALTIRE II: study investigating the effect of drugs used to treat osteoporosis on the progression of calcific aortic stenosis (NCT02132026); 4BASIK2: bicuspid aortic valve stenosis and the effect of vitamin K2 on calcium metabolism on 18F-NaF PET/MRI (NCT02917525); 5EvoLVeD: early valve replacement guided by biomarkers of LV decompensation …

Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p

Aortic valvular calcium score (AVCS) can identify severe aortic stenosis (AS) and provide powerful prognostic information. In severe and symptomatic AS, patients can be referred for a transcatheter aortic valve replacement (TAVR). The aim of this study was to determine whether AVCS, measured on the preoperative contrast enhanced multislice computed tomography (MSCT), is associated with device success (DS), major adverse cardiac events (MACEs) and paravalvular leak (PVL) after TAVR. Three hundred and fifty-two consecutive patients who underwent TAVR with a preoperative standardised contrast enhanced MSCT were included in the study. Valvular calcification detection was defined by adding + 100 Hounsfield Unit (HU) to mean HU determined by a region of interest placed in the contrast enhanced ascending aorta. AVCS was then indexed to the aortic annulus surface (AVCSi). Endpoints were DS and 30-day MACE according to Valve Academic Research Consortium-2 consensus document, and moderate to severe PVL. DS was obtained for 305 patients. In multivariate analysis, AVCSi was negatively and independently associated with DS: OR = 0.99, 95% CI 0.99–0.99, p = 0.03. In the subgroup analysis, this association was particularly relevant with self-expanding prostheses [n = 151 (43%), p = 0.018] and in the cases of asymmetric calcium valvular distribution [n = 283 (80%), p 0.002]. There was no association between MACE and AVCS (p = 0.953) and AVCSi (p = 0.757). PVL was positively associated with AVCS (p

Aim. To determine the inflammation and calcification activity in aortic stenosis (AS) by assessing the accumulation of 18F-FDG and 18F-NaF in the aortic valve; to study the relationship of the AS severity, aortic calcification and the accumulation of 18F-FDG and 18F-NaF. Material and methods. The study included 62 patients with asymptomatic AS (29 patients with tricuspid (TAV) and 33 with bicuspid (BAV) aortic valve), aged 40 to 70 years. The maximum flow rate at the aortic valve (Vmax) differs from 2,4 m/s to 4,5 m/s. The mean age of patients was 59,44±7,33 years, M:W 1:1. Patients with infective endocarditis and chronic rheumatic heart disease were excluded. The AS severity was assessed according to the standard protocol of transthoracic echocardiography with the use of Vivid 7 ultrasound system (GE,USA). All patients underwent combined positron emission tomography/computed tomography (PET/CT) of the aortic valve using the Discovery 710 system. Evaluation of calcification and inflammation activity of the aortic valve was performed using 8F-NaF and 18F-FDG PET/CT. A quantitative assessment of radiopharmaceuticals accumulation was carried out using uptake ratio indices. The calcium score was calculated using SmartScore 4.0 software.Results. Patients with TAV and BAV were comparable in severity of AS, the median Vmax was 2,9 [2,6; 3,4] m/s and 2,9 [2,3; 3,3] m/s, respectively. Also, TAV and BAV patients did not differ in calcification values (Agatston score 1088 [465; 2192] and 1128 [442; 2391] HU, respectively). The association of 18F-FDG accumulation and AS severity has not been established. At the same time, the association was found between the aortic valve peak velocity and the calcium score (r=0,57, p< 0,0001), as well as the 18F-NaF accumulation values — maximum, mean and maximum to mean (r=0,37, p=0,002; r=0,46, p=0,0001 and r=0,41, p=0,0008, respectively). No association between the accumulation of 18F-FDG and 18F-NaF (r=0,098, p=0,49) was found.Conclusion. It was found that the inflammation according to 18F-FDG PET/CT does not play a significant role in AS pathogenesis. At this time, 18F-NaF PET/CT is a reliable method for the AS diagnosis and valve calcification assessment. It can be used to evaluate the prognosis and effectiveness of therapy in TAV and BAV patients.

Currently, the only treatment for moderate and severe aortic valve calcification disease is valve replacement. The clinical use of bioprosthetic heart valves (BHVs) is limited because of device failure caused by structural degeneration, such as the calcification of BHV leaflets. In the present study, poly(ethylene glycol) diacrylate (PEGDA) was incorporated with zwitterion (2-[methacryloyloxy]ethyl)dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA) forming a balanced charged network, which was further used to modify decellularized heart valves (DHV) and improve anticalcification properties. Valvular prostheses were designed and manufactured to comply with the requirements of ISO-5840 for valve fluid dynamics (i.e., effective orifice area = 1.9 cm

Uptake of 18F-sodium fluoride (18F-NaF) on positron emission tomography (PET) reflects active calcification. Application of this technique in the early phase of aortic valve calcification (AVC) is of clinical interest. We investigated clinical implications of 18F-NaF uptake in subclinical AVC evaluated simultaneously with coronary atherosclerosis, and the utility of 18F-NaF uptake in predicting AVC progression. We studied 25 patients with subclinical AVC and coronary plaques detected on computed tomography (CT) who underwent 18F-NaF PET/CT. AVC score, volume, mean density, and the presence of high-risk coronary plaque were evaluated on CT in each patient. Focal 18F-NaF uptake in AVC and in coronary plaques was quantified with the maximum tissue-to-background ratio (TBRmax). There were positive correlations between AVC TBRmax (A-TBRmax) and AVC parameters on CT. The 14 patients with high-risk coronary plaque had significantly higher A-TBRmax than those without such plaque (1.60 ± 0.18 vs 1.42 ± 0.13, respectively; P = 0.012). A-TBRmax positively correlated with maximum TBRmax of coronary plaque per patient (r = 0.55, P = 0.0043). In the 11 patients who underwent follow-up CT scan, A-TBRmax positively correlated with subsequent increase in AVC score (r = 0.74, P = 0.0091). Our 18F-NaF PET- and CT-based data indicate relationships between calcification activity in subclinical AVC and characteristics of coronary atherosclerosis. 18F-NaF PET may provide new information regarding molecular conditions and future progression of subclinical AVC.

The first-line evaluation of aortic stenosis severity is Doppler echocardiography. However, in up to 40% of patients, resting echocardiographic assessment of aortic stenosis severity is discordant, leading to clinical uncertainty. Interest has therefore grown in aortic valve calcium scoring by multidetector computed tomography (CT-AVC) as an alternative load independent assessment of aortic stenosis severity. This paper will briefly review the pathophysiology of aortic stenosis and the crucial role that calcification plays in driving progressive obstruction of the valve. Subsequently, it will describe published reports that have investigated CT-AVC, validating this parameter against histology, and establishing its diagnostic accuracy versus echocardiography as well as its powerful independent prognostic capability. Finally, this review seeks to provide a practical guide about how best to acquire and interpret CT-AVC with a close focus on potential pitfalls and how these might be best avoided as this technique becomes more widely adopted in to clinical practice.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10–20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

Ectopic calcification of native and bioprosthetic heart valves represents a major public health problem causing severe morbidity and mortality worldwide. Valve procalcific degeneration is known to be caused mainly by calcium salt precipitation onto membranes of suffering non-scavenged cells and dead-cell-derived products acting as major hydroxyapatite nucleators. Although etiopathogenesis of calcification in native valves is still far from being exhaustively elucidated, it is well known that bioprosthesis mineralization may be primed by glutaraldehyde-mediated toxicity for xenografts, cryopreservation-related damage for allografts and graft immune rejection for both. Instead, mechanical valves, which are free from calcification, are extremely thrombogenic, requiring chronic anticoagulation therapies for transplanted patients. Since surgical substitution of failed valves is still the leading therapeutic option, progressive improvements in tissue engineering techniques are crucial to attain readily available valve implants with good biocompatibility, proper functionality and long-term durability in order to meet the considerable clinical demand for valve substitutes. Bioengineered valves obtained from acellular non-valvular scaffolds or decellularized native valves are proving to be a compelling alternative to mechanical and bioprosthetic valve implants, as they appear to permit repopulation by the host’s own cells with associated tissue remodelling, growth and repair, besides showing less propensity to calcification and adequate hemodynamic performances. In this review, insights into valve calcification onset as revealed by in vivo and in vitro procalcific models are updated as well as advances in the field of valve bioengineering.

Background Epicardial adipose tissue (EAT) exerts cardiopathogenic effects, but the independent association between EAT and cardiovascular (CV) calcification in patients with chronic kidney disease (CKD) remains controversial. We therefore assessed the association between EAT, CV risk factors and CV calcifications. Methods 257 patients with CKD Stage 3 and/or overt proteinuria underwent quantification of EAT, coronary artery calcification and aortic valve calcification by computed tomography. Framingham and American College of Cardiology and American Heart Association (ACC-AHA) 10-year CV event risk scores were calculated for each patient. Results Using multivariable regression analysis, higher EAT was significantly associated with the majority of investigated risk factors {higher age: odds ratio [OR] 1.05/year [95% confidence interval (CI) 1.02–1.08]; male sex: OR 4.03 [95% CI 2.22–7.31]; higher BMI: OR 1.28/kg/m2 [95% CI 1.20–1.37]; former smoking: OR 1.84 [95% CI 1.07–3.17]; lower high-density lipoprotein cholesterol: OR 0.98/mg/dL [95% CI 0.96–1.00] and lower estimated glomerular filtration rate: OR 0.98/mL/min/1.73 m2 [95% CI 0.97–0.99]; all P < 0.05} and was not associated with diabetes mellitus, hypertensive nephropathy, total cholesterol and albuminuria. EAT was positively associated with higher ACC-AHA and Framingham risk scores. EAT correlated with coronary artery calcification and aortic valve calcification [Spearman ρ = 0.388 (95% CI 0.287–0.532) and rrb = 0.409 (95% CI 0.310–0.556), respectively], but these correlations were dependent on CV risk factors. Conclusions The increase of EAT can be explained by individual CV risk factors and kidney function and correlates with 10-year risk for CV event scores, suggesting that EAT is a modifiable risk factor in patients with CKD. Although EAT correlates with CV calcifications, these relations depend on CV risk factors.

The mechanism of valve calcification, representing the main cause of aortic stenosis (AS) formation and progression still remains unclear. Currently, the role of the OPG/RANKL/RANK system is considered as one of important variants of valve calcification pathogenesis. In this study we have investigated the differences in the levels of OPG and sRANKL involved in the calcification processes in tissues of patients with severe AS. The study was performed on AS patients, on patients with aortic dilatation, and also on AS patients with aortic dilatation. Increased level of RANKL was found in AS patients and it was higher in valve than in aortic tissue. In patients with aortic dilatation the RANKL level negatively correlated with aortic dilatation. The results of this study confirm importance of the OPG/RANKL/RANK system for calcification in AS patients. Although patients of all groups had comparable values of OPG (including patients with aortic dilatation), increased RANKL level was found only in AS patients. This suggests involvement of some additional mechanisms influencing the increase of RANKL expression.

Aims: Direct oral anticoagulant (DOAC) has been recently introduced in the clinical practice. Rather than interfering with vitamin K-dependent posttranscriptional modification of various proteins, DOACs selectively inhibit factors involved in the coagulation cascade. In particular, in contrastwithWarfarin, Rivaroxabn does not interfere with activation of matrix Gla Protein (MGP), a potent vascular calcification Inhibitor. We herein sought to investigate the impact of Rivaroxaban and Warfarin on cardiac valve calcifications in a cohort of moderate-to advanced CKD patients. Methods and results: This is amulticenter, observational, retrospective, longitudinal study. Consecutive CKD stage 3b – 4 (according to KDIGO guidelines) patients from8 cardiologic outpatient clinicswere enrolled betweenMay 2015 and October 2017. All patients received anticoagulation (100Warfarin vs 247 Rivaroxaban) as part of their non-valvular atrial fibrillation management. Cardiac valve calcificationwas evaluated via standard trans-thoracic echocardiogram. 347 patients (mean age: 66 years;mean eGFR: 37 ml/min/1.73m2) were studied. Over a mean follow-up period of 16 months, Rivaroxaban compared toWarfarin reduced both mitral and aortic valve calcifications (p b 0.001) independently of the degree of calcifications at baseline and potential confounders. Notably, Rivaroxaban use was also associated with a significant reduction in C reactive protein (CRP) (p b 0.001) during follow-up. Conclusion: This study generates the hypothesis that the use of Rivaroxaban associateswith a reduction of cardiac valve calcification deposition and progression as compared to Warfarin, in a cohort of CKD stage 3b-4 patients. Future endeavors are needed to confirm and to establish the mechanisms responsible for these findings.

The early stages of aortic valve calcification (AVC) and coronary artery calcification (CAC) include shared ASCVD risk factors, yet there is considerable heterogeneity between the burden of AVC, and CAC. We sought to identify the markers associated with limited CAC among persons with significant AVC. There were 325 participants from the Multi-Ethnic Study of Atherosclerosis without clinical ASCVD and with AVC ≥100 Agatston units (AU) at Visit 1. Multivariable-adjusted prevalence ratios for limited CAC (0 to 99 AU) were calculated using modified Poisson regression. Participants had a mean age of 72.1 years, median AVC score of 209, and 34% were women. A total of 133 (41%) participants had CAC100, of whom 46/133 had CAC = 0. Younger age (PR = 1.40, 95% CI: 1.22 to 1.62, per 10-years), female gender (PR = 1.68, 95% CI: 1.28 to 2.20), and low 10-year ASCVD risk (PR = 2.30, 95% CI: 1.85 to 2.85) were most strongly associated with limited CAC. Neither a normal lipoprotein(a) nor normal measures of inflammation were significantly associated with limited CAC. Lower serum phosphate (PR = 1.15, 95% CI: 1.01 to 1.31; per 0.5 mg/dl lower) and calcium-phosphate product (PR = 1.16, 95% CI: 1.02 to 1.34; per SD lower) were associated with an approximately 15% higher prevalence of limited CAC. In conclusion, more than 40% of persons with significant AVC had CAC. Beyond traditional risk factors, lower serum phosphate, and lower calcium-phosphate product were associated with a higher prevalence of limited CAC.

Background: Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary-artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies.Purpose: To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations.Materials and Methods: A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed.Results: Overall, 594 participants (mean age. standard deviation, 62 years. 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years. 1.5). At baseline, the AVC score was 31 Agatston units. 117, and the normalized total plaque volume at baseline was 122 mm(3)+/- 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized. = 0.24; 95% CI: 0.16, 0.32; P..001) and both calcified (beta = 0.26; 95% CI: 0.18, 0.34; P