Valve Calcification Research Articles

The role of sclerostin in the formation of cardiovascular calcifi cation in chronic kidney disease C5D

THE AIM: to study the relationship of blood sclerostin with clinical parameters and its influence on the probability of detection of cardiovascular calcification in patients with CKD C5D. PATIENTS AND METHODS. The study was a single-stage, cohort study involving 84 patients with stage 5D CKD who received hemodialysis therapy, including 40 (47.6 %) female patients and 44 (52.4 %) male patients. The average age was 55.6±14.9 years. The examination included, in addition to routine studies, echocardioscopy with an assessment of calcification of the heart valves, abdominal radiography in the lateral projection with an assessment of aortic calcification, analysis of indicators that characterize phosphorus-calcium metabolism (serum sclerostin levels, 1.25(OH)D, FGF-23, A-klotho, PTH, P and Cа blood). Statistical analysis was performed using the computer program STATISTICA 12.6 (StatSoft Inc., USA). RESULTS. It was shown that the level of sclerostin is higher in the elderly, as well as those who have signs of hypoproteinemia and hypoalbuminemia, indirectly indicating the presence of protein-energy deficiency. There is an Association of blood sclerostin with FGF-23 and Alpha-klotho. From the point of view of the probable influence on the processes of cardiovascular calcification, this relationship shows its unidirectionality. Increased blood sclerostin levels have been shown to be associated with the risk of detecting signs of cardiovascular calcification. Moreover, it is shown that the higher the level of sclerostin in the blood, the more pronounced the degree of this calcification. Along with the increase in the level of sclerostin, the ability of a deficit of 1.25(OH)D to lead to the development of calcification was confirmed. CONCLUSION. A high level of sclerostin in the blood serum of more than 92.5 pmol / l in patients with CKD C5D increases the risk of detecting signs of cardiovascular calcification (calcification of the aortic wall and heart valves). An increase in sclerostin levels occurs in conjunction with an increase in FGF-23 and a decrease in 1.25(OH)D

High JAK2V617F variant allele frequency is associated with coronary artery but not aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms.

Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) have a higher burden of cardiac calcifications compared to the general population. It is not known whether the JAK2V617F mutation is associated with increased cardiac calcification. To investigate if a higher JAK2V617F variant allele frequency (VAF) is associated with severe coronary atherosclerosis and the presence of aortic valve calcification (AVC). Patients with MPNs were examined by cardiac computer tomography to establish coronary artery calcium score (CACS) and AVC score. The first VAF after diagnosis was registered. Severe coronary atherosclerosis was defined as a CACS >400 and AVC was defined as an AVC score >0. Among 161 patients, 137 were JAK2V617F mutation-positive, with a median VAF of 26% (interquartile range 12%-52%). A VAF in the upper quartile range was associated with a CACS >400 [odds ratio (OR) 15.96, 95% confidence interval [CI] 2.13-119.53, p = .0070], after adjustment for cardiovascular risk factors and MPN subtype. An association was not found for the presence of AVC (OR 2.30, 95% CI 0.47-11.33, p = 0.31). In patients with MPNs, there is a significant association between having a VAF in the upper quartile (>52%), and severe coronary atherosclerosis, defined as a CACS >400. The presence of AVC is not associated with VAF.

Comparison of Repair vs Replacement in Calcific and Rheumatic Mitral Disease

BackgroundThe benefit of repair over replacement of rheumatic or calcified mitral valve (MV) is debatable. MethodsPatients who underwent MV repair or replacement for rheumatic or calcified MV disease between 2006 and 2020 were identified in the Polish National Registry of Cardiac Surgery Procedures. Patients who underwent additional procedures other than coronary artery bypass grafting or tricuspid valve surgery, as well as redo or emergency cases, were excluded. The long-term survival was verified based on National Health Fund registry data. The survival was compared between MV repair and replacement in the whole cohort and after propensity score matching. ResultsWe included 4338 patients: 1859 (43%) with pure mitral regurgitation and 2479 (57%) with mitral stenosis. MV was repaired in 543 patients (29%) with pure regurgitation and 126 (5.1%) with stenosis (P < .001). In total, 984 (23%) patients underwent concomitant coronary artery bypass grafting and 1358 (32%) tricuspid valve surgery. MV repair improved survival (hazard ratio 0.81; 95% CI 0.68-0.97; P = .022) in patients with no mitral stenosis, and had no effect in mitral stenosis (hazard ratio 1.17; 95% CI 0.85-1.59; P = .332). The results were confirmed in propensity-matched cohorts. The freedom from MV reoperation at 10 years was 95.5% ± 1.2% after repair and 96.0% ± 0.7% after MV replacement (P = .416) in the absence of stenosis and 91.8% ± 3.4% after repair vs 95.9% ± 0.5% after replacement in patients with mitral stenosis (P = .065). ConclusionsRepair of rheumatic/calcified mitral valve should be a preferred option in patients with no mitral stenosis, but confers no benefit if mitral stenosis is present.

Hypoxia-inducible factor activation promotes osteogenic transition of valve interstitial cells and accelerates aortic valve calcification in a mice model of chronic kidney disease.

Valve calcification (VC) is a widespread complication in chronic kidney disease (CKD) patients. VC is an active process with the involvement of in situ osteogenic transition of valve interstitial cells (VICs). VC is accompanied by the activation of hypoxia inducible factor (HIF) pathway, but the role of HIF activation in the calcification process remains undiscovered. Using in vitro and in vivo approaches we addressed the role of HIF activation in osteogenic transition of VICs and CKD-associated VC. Elevation of osteogenic (Runx2, Sox9) and HIF activation markers (HIF-1α and HIF-2α) and VC occurred in adenine-induced CKD mice. High phosphate (Pi) induced upregulation of osteogenic (Runx2, alkaline-phosphatase, Sox9, osteocalcin) and hypoxia markers (HIF-1α, HIF-2α, Glut-1), and calcification in VICs. Down-regulation of HIF-1α and HIF-2α inhibited, whereas further activation of HIF pathway by hypoxic exposure (1% O2) or hypoxia mimetics [desferrioxamine, CoCl2, Daprodustat (DPD)] promoted Pi-induced calcification of VICs. Pi augmented the formation of reactive oxygen species (ROS) and decreased viability of VICs, whose effects were further exacerbated by hypoxia. N-acetyl cysteine inhibited Pi-induced ROS production, cell death and calcification under both normoxic and hypoxic conditions. DPD treatment corrected anemia but promoted aortic VC in the CKD mice model. HIF activation plays a fundamental role in Pi-induced osteogenic transition of VICs and CKD-induced VC. The cellular mechanism involves stabilization of HIF-1α and HIF-2α, increased ROS production and cell death. Targeting the HIF pathways may thus be investigated as a therapeutic approach to attenuate aortic VC.

P81: Development Of A Pre-Operative Planning Tool For Patients With Mitral Regurgitation

Mitral regurgitation is the most frequent valve disease in patients over the age of 65 years. In patients with high surgical risk, transcatheter mitral valve intervention (TMVI) is the preferred therapy. However, patient selection for this therapy remains a challenge. This study aims at developing a simulation tool to assist surgeons pre-operatively to choose the treatment based on the patient’s characteristics. In this study, a clinical data (echocardiography and CT scans) of a TMV recipient with a history of severe mitral calcification was considered. Left ventricular (LV) and mitral valve (MV) models were obtained from pre-TMVI CT scans. Pre- and post-TMVI hemodynamics were generated by a lumped-parameter model which were then applied as boundary conditions for two fluid–structure interaction (FSI) simulations with contractile LV and dynamic MV; first, a pre-TMVI simulation with the anatomical MV model and second, a post-TMVI simulation with a Tendyne transcatheter mitral valve model. Mitral pressure gradients (MPG) and effective orifice area (EOA) were calculated. The predictions of the pre-TMVI simulations closely resembled Echo data. Calcified mitral leaflets led to a narrowing of the diastolic opening area resulting in an increased pressure gradient over the MV; EOA (FSI: 2.1 cm2, ECHO: 1.9 cm2), MPG (FSI: 3.8 mmHg, ECHO: 3.4mmHg). These values improved significantly for the post-TMVI simulation (EOA: 4.5 cm2, MPG: 1.1 mmHg), Figure 1. By combining medical imaging and computer modeling, we established a validated tool that can be used pre-TMVI to assist clinicians to select the optimal therapy based on patients’ characteristics.Figure 1. Pre-, and post-TMVI simulation of a patient with severely calcified mitral valve; TMVI: transcatheter mitral valve intervention

BIO3: Advancement of a Novel Polymeric Transcatheter Aortic Valve as an Alternative to Tissue-based Valves

Background: Transcatheter aortic valve replacement (TAVR) is a minimally invasive alternative to surgical valve replacement, originally targeted to elderly patients with aortic stenosis (AS), now increasingly utilized in younger lower risk AS patients. With growth of TAVR the shortcomings of current tissue-based valves are becoming prevalent, namely limited durability and thromboembolic risk. To address these, a polymeric TAV named PolyV-2 (27 mm, PolyNova Cardiovascular Inc, Stony Brook, NY) was designed, optimized, and further tested. Methods: The design of the PolyV-2 (Figure A) was achieved with a battery of in silico simulations including the use of finite element analysis (FEA, Abaqus 2020, Dassault Systems, Providence, RI) to optimize the radial force of the stent frame and minimize leaflet stresses during the cardiac cycle. The PolyV-2 employs a sutureless design via coating the stent with polymer, bypassing problematic hand suturing manufacture of tissue valves. The PolyV-2 utilizes a thermoplastic elastomer polymeric material which was tested in vitro with accelerated wear durability testing according to ISO 5840-3 (2015) with periodic performance testing, evaluated against tissue-based surgical and TAV devices for platelet activation rate (PAR) in a pulsatile flow loop, and evaluated for calcification risk with similar wear testing in a pro-calcific medium. To assess the deposition of calcifications in the valves, both µCT and ICP spectroscopy were used. Results: The optimization process of the PolyV-2 leaflets (Figure B) was able to greatly lower the peak and mean stresses throughout over the cardiac cycle by employing a variable thickness across the entire leaflet. With success of this in silico optimization process, the leaflets were then tested in vitro (Figure C) in accelerated wear testing, performing 1Billion cycles w/o failure – correlating to 25 years of efficacy in vivo, exceeding the 250 million minimum required by the FDA. The material also demonstrated favorable hemocompatiblity as to PAR (Figure D) with activation significantly lower than a commercial tissue TAVR device, more comparable to a surgical device. The pro-calcific wear testing demonstrated no deposition of calcific salts within the polymer leaflet (µCT image, Figure E) compared to the tissue valve and minimal calcium detected with ICP spectroscopy. Conclusion: To mitigate the persistent complications of tissue-based TAV devices, the polymeric PolyV-2 valve was optimized through a battery of in silico and in vitro trials to offer superior hemodynamics, performance, and durability. Proper design and material considerations are essential to ensure successful translation, demonstration of enhanced bio/hemocompatibility and advance of the PolyV-2 through in vivo animal trials.

Overview of the Use of CUSA as a Novel Technique to Aid in Annular Decalcification

Mitral annular calcification (MAC) is a major complicating factor in cardiac valve surgery, leading to increased difficulty and complexity in valve replacement. Utilisation of the Cavitron Ultrasonic Surgical Aspirator (CUSA) for annular decalcification has facilitated successful surgical intervention in the setting of severe calcific valve disease in patients who may have otherwise been deemed inoperable or had unsatisfactory surgical outcomes.

Target Aortic Stenosis: A National Initiative to Improve Quality of Care and Outcomes for Patients With Aortic Stenosis.

Target Aortic Stenosis: A National Initiative to Improve Quality of Care and Outcomes for Patients With Aortic Stenosis.

Cardiac Virtual Noncontrast Images for Calcium Quantification with Photon-counting Detector CT

Purpose To assess the accuracy of aortic valve calcium (AVC), mitral annular calcium (MAC), and coronary artery calcium (CAC) quantification and risk stratification using virtual noncontrast (VNC) images from late enhancement photon-counting detector CT as compared with true noncontrast images. Materials and Methods This retrospective, institutional review board–approved study evaluated patients undergoing photon-counting detector CT between January and September 2022. VNC images were reconstructed from late enhancement cardiac scans at 60, 70, 80, and 90 keV using quantum iterative reconstruction (QIR) strengths of 2–4. AVC, MAC, and CAC were quantified on VNC images and compared with quantification of AVC, MAC, and CAC on true noncontrast images using Bland-Altman analyses, regression models, intraclass correlation coefficients (ICC), and Wilcoxon tests. Agreement between severe aortic stenosis likelihood categories and CAC risk categories determined from VNC and true noncontrast images was assessed by weighted κ analysis. Results Ninety patients were included (mean age, 80 years ± 8 [SD]; 49 male patients). Scores were similar on true noncontrast images and VNC images at 80 keV for AVC and MAC, regardless of QIR strengths, and VNC images at 70 keV with QIR 4 for CAC (all P > .05). The best results were achieved using VNC images at 80 keV with QIR 4 for AVC (mean difference, 3; ICC = 0.992; r = 0.98) and MAC (mean difference, 6; ICC = 0.998; r = 0.99), and VNC images at 70 keV with QIR 4 for CAC (mean difference, 28; ICC = 0.996; r = 0.99). Agreement between calcification categories was excellent on VNC images at 80 keV for AVC (κ = 0.974) and on VNC images at 70 keV for CAC (κ = 0.967). Conclusion VNC images from cardiac photon-counting detector CT enables patient risk stratification and accurate quantification of AVC, MAC, and CAC. Keywords: Coronary Arteries, Aortic Valve, Mitral Valve, Aortic Stenosis, Calcifications, Photon-counting Detector CT Supplemental material is available for this article © RSNA, 2023

On the spectrum of transcatheter mitral valve replacement: In silico and in vitro assessment of neo-LVOT area in ViR, ViV and ViMAC

The assessment of the neo-left ventricular outflow tract (neo-LVOT) area is an essential metric for pre-procedural imaging when screening patients for transcatheter mitral valve replacement (TMVR) eligibility. Indeed, the implantation of transcatheter heart valves for treating failed annuloplasty band ring (ViR), bioprosthesis (ViV) and mitral valve calcification (ViMAC) can lead to a permanent obstruction of the implanted device (namely, LVOT obstruction). In this study, in silico computational modeling and 3D printing were used to quantify the neo-LVOT area and the resulting hemodynamic outcomes of TMVR. We first simulated the deployment of the SAPIEN 3 Ultra device (Edwards Lifesciences, Irvine, CA) and then evaluated the pressure drop near the LVOT obstruction using computational fluid dynamics. The neo-LVOT area was largest in patients with ViR (453.4 ± 58.1 mm2) compared to patients with ViV (246.6 ± 109.5 mm2) and ViMAC (155.6 ± 46.1 mm2). The pressure drop near the LVOT obstruction differed among patients with TMVRs and significantly correlated with the magnitude of the neo-LVOT area (R = −0.761 and P-value = 0.047). The present study highlights the potential of in silico and 3D printed models for planning TMVR procedures and for carrying out a risk evaluation of the device protrusion into the left heart when treating failed mitral valves.

Surgical outcomes of aortic valve repair for specific aortic valve cusp characteristics; retraction, calcification, and fenestration

ObjectivesWe investigated the predictive value of aortic valve cusp retraction, calcification, and fenestration for aortic valvuloplasty feasibility. MethodsMulticenter data were collected for 2082 patients who underwent surgical aortic valvuloplasty or aortic valve replacement. The study population had retraction, calcification, or fenestration in at least one aortic valve cusp. Controls had normal or prolapsed cusps. ResultsAll cusp characteristics demonstrated significantly increased odds ratios [ORs] for switch to valve replacement. This effect was strongest for cusp retraction, followed by calcification and fenestration (OR, 25.14; P ≤ .001; OR, 13.50, P ≤ .001; OR, 12.32, P ≤ .001). Calcification and retraction displayed increased odds for developing grade 4 aortic regurgitation compared with grade 0 or 1 combined on average over time (OR, 6.67; P ≤ .001; OR, 4.13; P = .038). Patients with cusp retraction showed increased risk for reintervention at 1- and 2-year follow-up after aortic valvuloplasty (hazard ratio, 5.66; P ≤ .001; hazard ratio, 3.22, P = .007). Cusp fenestration was the only group showing neither an increased risk of postoperative severe aortic regurgitation (P = .57) or early reintervention (P = .88) compared with the control group. ConclusionsAortic valve cusp retraction, calcification, and fenestration were all related to increased rates of switch to valve replacement. Calcification and retraction were associated with recurrence of severe aortic regurgitation. Retraction was related to early reintervention. Fenestration was neither associated with recurrence of severe aortic regurgitation or reintervention. This indicates that surgeons are well able to distinguish aortic valve repair candidates in patients with cusp fenestration.

Overexpression of microRNA-93-5p and microRNA-374a-5p Suppresses the Osteogenic Differentiation and Mineralization of Human Aortic Valvular Interstitial Cells Through the BMP2/Smad1/5/RUNX2 Signaling Pathway.

Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate-induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium-phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.

IL-17A induces valvular endothelial inflammation and aggravates calcific aortic valve disease

Calcific aortic valve disease (CAVD) is an aging related disease characterized by inflammation and fibrocalcific remodeling. IL-17A is a key cytokine associated with pathophysiology of inflammatory and fibrotic disease. Previous studies showed accumulation of IL-17A-producing T helper lymphocytes in human calcified aortic valves and significantly elevated IL-17RA expression in calcified valves. However, the role of IL-17A signaling in the initiation and development of CAVD is still unclear. In this study, by analyzing public transcriptome databases, we found that IL-17A-IL-17RA signaling is activated in calcified valves. Gene expression analysis revealed significantly increased IL-17A, IL-17RA, and RUNX2 expression in calcified human aortic valves compared to in non-calcified valves, and the expression of IL-17A and IL-17RA were positively correlated with RUNX2 expression. A 5/6 nephrectomy was performed in Apoe−/− (Apoe knockout) mice to establish a CAVD mouse model. IL-17A-neutralizing antibodies significantly reduced valve calcium deposition and decreased expression of RUNX2 in aortic valves. Immunofluorescence staining of human aortic valves and qRT-PCR analysis of primary aortic valve cells revealed abundant expression of IL-17RA in valvular endothelial cells (VECs). RNA sequencing indicated that IL-17A promoted the activation of inflammatory signaling pathways in VECs. Furthermore, qRT-PCR and cytometric bead array analysis confirmed that IL-17A promoted the expression or secretion of inflammatory cytokines IL-6 and IL-1β, chemokines CXCL2 and CXCL8, and fibrosis-related gene COL16A1. Our findings indicate that elevated IL-17A in CAVD may promote valve inflammation, fibrosis, and calcification by inducing endothelial activation and inflammation. Targeting IL-17A-IL-17RA signaling may be a potential therapeutic strategy for CAVD.

“UFO procedure” for massive aortic and mitral annular calcification involving left atrial and ventricular myocardium: a potential radical solution

BackgroundThe “UFO procedure” was initially developed as a surgical option to enlarge the aortic annulus in patients requiring valve replacement. This technique can be employed to treat extensive endocarditis located in the intervalvular fibrous body (IVFB). One of the indications for a "UFO procedure" is massive aortic and mitral valve calcification. It is a challenging surgical procedure with a high risk of intraoperative complications.Case summaryWe present a 76-year-old male patient with massive aortic and mitral valve calcification involving the left atrium, the left ventricle and the left ventricular outflow tract. Both valves exhibited severe stenosis and moderate to severe regurgitation. The left ventricle was hypertrophic and the left ventricular ejection fraction was > 55%. The patient was prediagnosed with persistent atrial fibrillation. The risk of death following heart surgery (EuroSCORE II) was calculated as 9.21%. We successfully performed a so-called “UFO procedure” including replacement of both valves without annular decalcification to avoid atrioventricular dehiscence. We enlarged the IVFB and replaced the non-coronary sinus of Valsalva with doubled bovine pericardium. The left ventricular outflow tract was decalcified. The patient was transferred to a local hospital on the 13th postoperative day.ConclusionSuccessful surgical treatment to this extent was demonstrated for the first time. Due to the high perioperative mortality, the surgical treatment of patients with this constellation would be refused in most cases. In our patient, the preoperative imaging showed extreme calcification of both valves and the surrounding myocardium. Excellent preoperative planning and a highly experienced surgical team is necessary.

Quantity and location of aortic valve calcification predicts paravalvular leakage after transcatheter aortic valve replacement: a systematic review and meta-analysis.

Transcatheter aortic valve replacement (TAVR) is the first-line treatment for patients with moderate-to-high surgical risk of severe aortic stenosis. Paravalvular leakage (PVL) is a serious complication of TAVR, and aortic valve calcification contributes to the occurrence of PVL. This study aimed to investigate the effect of location and quantity of calcification in the aortic valve complex (AVC) and left ventricular outflow tract (LVOT) on PVL after TAVR. We performed a systematic review and meta-analysis to evaluate the effect of quantity and location of aortic valve calcification on PVL after TAVR using observational studies from PubMed and EMBASE databases from inception to February 16, 2022. Twenty-four observational studies with 6,846 patients were included in the analysis. A high quantity of calcium was observed in 29.6% of the patients; they showed a higher risk of significant PVL. There was heterogeneity between studies (I2 = 15%). In the subgroup analysis, PVL after TAVR was associated with the quantity of aortic valve calcification, especially those located in the LVOT, valve leaflets, and the device landing zone. A high quantity of calcium was associated with PVL, regardless of expandable types or MDCT thresholds used. However, for valves with sealing skirt, the amount of calcium has no significant effect on the incidence of PVL. Our study elucidated the effect of aortic valve calcification on PVL and showed that the quantity and location of aortic valve calcification can help predict PVL. Furthermore, our results provide a reference for the selection of MDCT thresholds before TAVR. We also showed that balloon-expandable valves may not be effective in patients with high calcification, and valves with sealing skirts instead of those without sealing skirts should be applied more to prevent PVL from happening. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354630, identifier: CRD42022354630.

Diagnostic role of aortic valve calcium scoring in various etiologies of aortic stenosis

Most of the studies about aortic valve calcium (AVC) score in aortic stenosis (AS) were based on degenerative or bicuspid AS but not rheumatic AS. We aimed to study the diagnostic accuracy of AVC score to determine severe AS in various etiologies. Adult patients diagnosed with mild to severe AS were enrolled. AVC score were identified from multi-detector computed tomography (MDCT) scan. The AVC score was highest in bicuspid AS (3211.9 (IQR (1100.0–4562.4) AU) compared to degenerative AS (1803.7 (IQR (1073.6–2550.6) AU)), and rheumatic AS (875.6 (IQR 453.3–1594.0) AU), p < 0.001. For the ROC curve to identify severe AS, the AVC score performed well in degenerative and bicuspid AS with the area under the ROC curve (AuROC) 0.834 (95% CI, 0.730, 0.938) in degenerative group; and 0.820 (95% CI, 0.687, 0.953) in bicuspid AS. Whereas AVC score had non-significant diagnostic accuracy with AuROC 0.667 (95% CI, 0.357, 0.976) for male and 0.60(95% CI, 0.243, 0.957) for female in rheumatic AS. The cut-off AVC score values to identify severe AS were AVCS > 2028.9AU (male) and > 1082.5AU (female) for degenerative AS, and > 2431.8AU (male) and > 1293.5AU (female) for bicuspid AS. In conclusions, AVC score is the accurate test for assessing severity in patients with degenerative and bicuspid AS but performs poorly in rheumatic AS group.

Surgery for mitral annular caseous calcification-related calcified amorphous tumor: a case report

BackgroundA calcified amorphous tumor (a non-neoplastic tumor) with caseous calcification of the mitral annulus is a rare pathology that causes severe embolic events. We present a rare case of mitral valve surgery for a mitral annular caseous calcification-related calcified amorphous tumor found in cerebral infarction.Case presentationA 69-year-old man was diagnosed with a mitral valve calcified amorphous tumor with mitral annular caseous calcification found in cerebral infarction. He was admitted because of acute multiple embolic cerebral infarctions. A search for the embolic source through transesophageal echocardiography revealed a mitral valve tumor raised from the posterior mitral valve leaflet on the side of the left ventricle. Computed tomographic cardiac angiography revealed a calcified mitral valve tumor invading the posterior mitral valve annulus and left ventricular muscle. Intraoperative findings revealed a mitral annular calcification-related calcified amorphous tumor with caseous calcification of the posterior leaflet and annulus, which was suspected. Therefore, we performed radical debridement of the mitral annular calcification and bioprosthetic mitral valve replacement with patch repair of the posterior mitral valve annulus 2 weeks after the onset of cerebral infarction. The patient recovered well post operation, without any embolic events.ConclusionsA calcified amorphous tumor with caseous mitral annulus calcification may be highly associated with embolic events. In this case, mitral valve replacement with annular patch repair may be a favorable procedure for preventing embolic events.

Ultra-low radiation dose and contrast volume CT protocol and TAVI-CT score for TAVI planning and outcome.

To investigate the feasibility of an ultra-low radiation dose and contrast volume protocol using third-generation dual-source (DS) CT for transcatheter aortic valve implantation (TAVI) planning with coronary artery disease (CAD) assessment, coronary artery calcium score (CACS) and aortic valve calcium score (AVCS) quantification and to evaluate their relationship with TAVI outcome. In this retrospective study were selected 203 patients (131 males, 79.4 ± 5.4 years) underwent to TAVI and at 30- and 90-day follow-up. All patients had performed a third-generation 2 × 192-slices DSCT. The CT protocol included a non-contrast and a contrast high-pitch aortic acquisition for TAVI planning and CAD assessment. Semi-qualitative and quantitative image analysis were performed; the performance in CAD assessment was compared with ICA; the relationship between AVCS and CACS and paravalvular aortic regurgitation (PAR) and major cardiovascular events (MACEs) were evaluated. Mean radiation dose were calculated. Non-parametric tests were used. Semi-qualitative image analysis was good. Contrast enhancement >500 Hounsfield unit (HU) and contrast-to-noise ratio <20 were obtained in all segments. The diagnostic accuracy in CAD was 89.0%. AVCS was significantly higher in patients with 30-day severe PAR. AVCS and CACS were higher in patients with 90-day MACE complications, respectively, 1904.5 ± 621.3 HU (p < 0.0001) and 769.2 ± 365.5 HU (p < 0.0230). Mean radiation dose was 2.8 ± 0.3 mSv. A TAVI planning ultra-low radiation dose and contrast volume protocol using third-generation DSCT provides highly diagnostic images with CAD assessment, AVCS and CACS quantification and these latter were related with TAVI outcomes. The proposed protocol using third-generation 2 × 192-slices DSCT allows with an ultra-low radiation dose and contrast volume the TAVI planning and the coronary artery assessment.

Aortic valve calcification of surgical bioprostheses and its impact on clinical outcome

Aortic valve calcification (AVC) of surgical valve bioprostheses (BP) has been poorly explored. We aimed to evaluate in vivo and ex vivo BP AVC and its prognosis value. Between 2011 and 2019, AVC was assessed in 361 patients with surgical BP on in vivo computed tomography (CT) scanner (6.4 ± 4.3 years after surgery). Follow-up was obtained in all patients. Ex vivo CT-scans were performed in 37 explanted BP. After exclusion of 19 (5.2%) CT-scans, mean in vivo AVC was 307 ± 500 AU in the remaining 342 BP (77 ± 9 years, 64% male). Of these, 183 (53.5%) had a structural valve degeneration (SVD) with an AVC of 562 ± 570 AU compared with 13 ± 43 AU (P < 0.0001) for non-SVD BP. Early calcification was observed in around 10% of BP (12/124) examined before the 3rd postoperative year. In explanted BP in vivo AVC correlated strongly with ex vivo AVC (r = 0.88, P < 0.0001). An in vivo AVC > 100 AU (n = 147, 43%) had an excellent specificity (96%) for diagnosing stage 2–3 SVD. Patients with AVC > 100 AU had worse survival compared with those with an AVC < 100 (n = 195, 57%). In multivariable analyses, AVC value was a predictor of overall mortality (HR = 1.16 [1.04–1.29]; P = 0.009), cardiovascular mortality (HR = 1.21 [1.03–1.41]; P = 0.021) and cardiovascular events (HR = 1.19 [1.08–1.31]; P = 0.001). After further adjustment for SVD diagnosis, AVC remained a predictor of overall mortality (HR = 1.24 [1.07–1.44]; P = 0.005), and cardiovascular events (HR = 1.16 [1.02–1.32]; P = 0.029). CT-scan AVC of surgical BP is a reliable tool for assessing leaflets calcification. Whereas calcification can develop early after surgery, an AVC > 100 AU is tightly associated with SVD, and is a strong predictor of overall mortality and cardiovascular events, even after adjustment for SVD diagnosis. Hence, AVC scoring is a complementary tool to echocardiography that should be used in the follow-up of patients with surgical aortic BP.

Identification of TNFα-mediated inflammation as potential pathological marker and therapeutic target for calcification progress of congenital bicuspid aortic valve

BackgroudCongenital bicuspid aortic valve (cBAV) develops calcification and stenotic obstruction early compared with degenerative tricuspid aortic valve (dTAV), which requires surgical intervention. Here we report a comparative study of patients with cBAV or dTAV to identify risk factors associated with the rapid development of calcified bicuspid valves. MethodsA total of 69 aortic valves (24 dTAV and 45 cBAV) were collected at the time of surgical aortic valve replacement for comparative clinical characteristics. Ten samples were randomly selected from each group for histology, pathology, and inflammatory factors expression and comparison analyses. OM-induced calcification in porcine aortic valve interstitial cell cultures were prepared for illustrating the underlying molecular mechanisms about calcification progress of cBAV and dTAV. ResultsWe found that cBAV patients have increased cases of aortic valve stenosis compared with dTAV patients. Histopathological examinations revealed increased collagens deposition, neovascularization and infiltrations by inflammatory cells, especially T-lymphocytes and macrophages. We identified that tumor necrosis factor α (TNFα) and its regulated inflammatory cytokines are upregulated in cBAV. Further in vitro study indicated that TNFα-NFκB and TNFα-GSK3β pathway accelerate aortic valve interstitial cells calcification, while inhibition of TNFα significantly delays this process. ConclusionThe finding of intensified TNFα-mediated inflammation in the pathological cBAV advocates the inhibition of TNFα as a potential treatment for patients with cBAV by alleviating the progress of inflammation-induced valve damage and calcification.