Degenerative Aortic Valve Research Articles

Bioprosthetic aortic valve degeneration evaluated by 18F-fluoride PET-TC

Abstract Background Implantation of bioprosthetic aortic valves (BPHV) is increasing owing to the aging population and the emergence of transcatheter aortic valve implantation. Along with the increase in life expectancy, BPHV degeneration is therefore becoming an increasing problem. 18F-fluoride positron emission tomography (PET) has emerged as a method that could identify early subclinical BPHV degeneration. Purpose We aimed to compare early PET parameters of fluorid uptake with echocardiographic hemodynamic parameters at three years after the implantation of a bioprosthetic aortic valve. Methods Sub-analysis of the ANTIPRO clinical trial. Patients undergoing aortic valve replacement (AVR) for porcine bioprosthesis were recruited at two surgical centers between 01/01/2019 and 02/13/2020, and were randomized in two groups (acetylsalicylic acid (ASA) vs ASA and oral anticoagulation for 3 months). Clinical and echocardiographic controls were performed one year and three years after AVR. Bioprosthetic valve deterioration (BVD) was defined according to the Valve Academic Research Consortium 3. 43 subjects were randomly selected from the whole cohort to undergo 18F-sodium fluoride PET with CT angiography (PET-CT) at follow-up. 18F-fluoride uptake in the valve (SUVavV) and right atrium (SUVavA) was measured, creating the SUVavV/SUVavA ratio or target-to-background ratio (TBR). PET findings were categorized as "high uptake" if TBR > 1.3 and "low uptake" if TBR ≤1.3. TBR was compared with the mean and maximum gradients at three years. Survival between high and low uptake groups was calculated using Kaplan-Meier and compared with log-rank test. The project was approved by the national ethics committee and patients consented the procedure. Results 18F-sodium fluoride PET-CT was performed on 43 subjects, with a mean time of 22.7±8.4 months after AVR. The echocardiogram at three years was performed in a mean time of 39.9±3.0 months after AVR. Mean time between PET-CT and echocardiogram was 17.2±9.9 months. The mean TBR was 1.25±0.30. Low uptake was found in 27 patients (62.8%) and high uptake in 15 patients (34.9%). Uptake could not be quantified in one patient due to technical problems. Baseline characteristics were similar between both groups (Table 1). Mean gradient at three years was 19.6±10.3 and peak gradient 33.7±16.7. Mean gradient was similar between the high uptake and low uptake groups (17.5±11.7 vs 21.6±9.3 p=0.296). Peak gradient was also similar between the high uptake and low uptake groups (30.6±18.5 vs 36.3±15.6 p=0.362). Five patients experienced BVD, of which 4 had low uptake and 1 had high uptake (p=0.523). Survival analysis did not demonstrate statistically different survival rates between the high uptake and low uptake groups (Figure 1). Conclusion Fluorid uptake with early PET after AVR was not associated with trans-prosthetic gradients nor BVD after a mean of 17 months from the PET scan.Table 1:Baseline characteristicsFigure 1:Kaplan-Meier survival curve

Abstract 15962: Validation of the Senescence-Associated Secretome to Predict Mortality in Patients With Degenerative Aortic Valve Stenosis

Introduction: The senescence-associated secretory phenotype (SASP) is a potential driver of age-related risk reflecting advanced biological aging. Circulating SASP components include pro-inflammatory cytokines, growth modulators and matrix remodelling proteases. Aortic valve stenosis (AVS) is the prototypical inflammatory age-associated cardiovascular disease. Hypothesis: To identify circulating SASP components with an impact on prognosis in elderly pts with AVS. Methods: In a derivation cohort (n=120), circulating levels of 24 SASP components were measured using Luminex Multiplex ELISA, before undergoing TAVR. ROC curves and Youden-index derived optimal cut-off values were used to assess the predictive power of each SASP for long-term mortality. In a validation cohort (n=198), the significant predictors of mortality identified in the derivation cohort, as well as a panel of 3 independent predictors in multivariate analyses, were prospectively validated. Results: In the derivation cohort, 9 out of 24 SASP components significantly predicted mortality in univariate analyses with AUC>0.62; only 3 (GDF-15, ICAM-1, and osteoprotegerin) remained independent predictors in multivariate analyses (all p<0.03). All 3 were confirmed as significant independent predictors of mortality in the validation cohort (see AUC curves). After adjustment for clinical parameters, a score based on the cumulative number of these 3 SASP components showed a substantial increase in long-term mortality after TAVR for each additional positive marker (see KM-curves). Conclusions: This study validates high levels of 3 SASP components reflecting different pathophysiological pathways of senescence as independent predictors of long-term mortality in AVS. Their cumulative occurrence provides a deeply improved discrimination power and, may serve as a much needed risk stratification tool in elderly patients with AVS undergoing TAVR.

Abstract 12257: The Relationship Between Histological Features of Epicardial Adipose Tissue and Aortic Valve Calcification Assessed on Computed Tomography

Background: It has been hypothesized that epicardial adipose tissue (EAT) biologically contributes to the pathogenesis of cardiac diseases. However, it remains unclear how EAT correlates with the progression of aortic valve calcification (AVC). We evaluated if histological features of EAT are specifically related to AVC assessed on computed tomography (CT). Methods: We enrolled 35 patients undergoing cardiac CT examination before elective cardiac surgery (coronary artery bypass graft [CABG] and/or cardiac valve surgery), in which AVC was detected on CT. Each patient was evaluated with EAT volume, coronary calcium score (CCS), AVC score, and the presence of high-risk coronary plaque (HRP) on CT. During each cardiac surgery, histological samples for immunohistochemistry were obtained from EATs adjacent to the left anterior descending and right coronary arteries. Each patient was assessed with the numbers of CD-68 + and CD-11c + individual macrophages and osteocalcin + individual cells in a total of 6 random high-power fields (x400) of EAT samples. Results: In the histological findings of EAT, osteocalcin + cells showed a weak correlation with CD-68 + macrophages ( r = 0.40, p = 0.016) and a moderate correlation with CD-11c + macrophages ( r = 0.60, p = 0.0001). The AVC score on CT correlated with CD-11c + macrophages and osteocalcin + cells in EAT (Fig 1), whereas CCS had no correlation with such histological findings. On multivariate analysis adjusted for age, sex, CABG vs. non-CABG, EAT volume, CCS, and the presence of HRP, the AVC score independently correlated with increased CD-11c + macrophages (β = 0.58; p = 0.0036) and osteocalcin + cells (β = 0.59; p = 0.0021) in EAT. Fig 2 shows representative cases with different levels of AVC and EAT histology. Conclusions: The inflammatory and osteogenic activity in EAT significantly correlate with the progression of AVC, which may indicate a specific contribution of EAT to aortic valve degeneration through biological activities.

Diabetes-induced aortic valve degeneration in static cultivation and in a bioreactor system

Diabetes-induced aortic valve degeneration in static cultivation and in a bioreactor system

Hydrogen sulfide inhibits gene expression associated with aortic valve degeneration by inducing NRF2-related pro-autophagy effect in human aortic valve interstitial cells.

Aortic valve stenosis (AS) is the most common valvular heart disease but there are currently no effective medical treatments that can delay disease progression due to a lack of knowledge of the precise pathophysiology. The expression of sulfide: quinone oxidoreductase (SQOR) and nuclear factor erythroid 2-related factor 2 (NRF2) was decreased in the aortic valve of AS patients. However, the role of SQOR and NRF2 in the pathophysiology of AS has not been found. We investigated the effects of hydrogen sulfide (H2S)-releasing compounds on diseased aortic valve interstitial cells (AVICs) to explain the cellular mechanism of SQOR and elucidate the medical value of H2S for AS treatment. Sodium hydrosulfide (NaHS) treatment increased the expression of SQOR and NRF2 gene and consequently induced the NRF2 target genes, such as NAD(P)H quinone dehydrogenase 1 and cystathionine γ-lyase. In addition, NaHS dose-dependently decreased the expression level of fibrosis and inflammation-related genes (MMP9, TNF-α, IL6) and calcification-related genes (ALP, osteocalcin, RUNX2, COL1A1) in human AVICs. Furthermore, NaHS activated the AMPK-mTOR pathway and inhibited the PI3K-AKT pathway, resulting in a pro-autophagy effect in human AVICs. An NRF2 inhibitor, brusatol, attenuated NaHS-induced AMPK activation and decreased the autophagy markers Beclin-1 and LC3AB, suggesting that the mechanism of action of H2S is related to NRF2. In conclusion, H2S decreased gene expression levels related to aortic valve degeneration and activated AMPK-mTOR-mediated pro-autophagy function associated with NRF2 in human AVICs. Therefore, H2S could be a potential therapeutic target for the development of AS treatment.

Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach

BackgroundDiabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM.Methods283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed.ResultsOxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules.ConclusionsDM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women.

The Role of Advanced Glycation End-Product Levels Measured by Skin Autofluorescence in the Development of Mitral Annular Calcification.

As a person ages, mitral annular calcification develops in the mitral annulus with increasing frequency. Lipid deposition, inflammation, and aging-related degeneration have been cited as potential causes of this pathophysiology, though there is currently no conclusive evidence to support this. AGEs accumulate in tissues due to the glycation of proteins and lipids, increasing the release of proinflammatory cytokines secondary to oxidative stress through the AGE receptor. The AGE levels increase in diabetic microvascular complications and degenerative aortic valve disease. Our study was planned prospectively as a case-control study involving 94 MAC-positive patients and 94 MAC-negative patients. The demographics, echocardiographic data and AGE levels of the patients were measured and recorded using the skin autofluorescence method. AGE levels were significantly higher in the MAC-positive patient group (3.2 vs. 2.7; p < 0.001). The AGE levels were observed as an independent predictor of MAC development in a regression analysis (OR: 8.05, 95% CI: 3.74-17.33, p < 0.001). In a ROC-curve analysis, the AUC was 0.79 (95% CI: 0.72-0.85). At a cut-off value of 2.7, 79.7% sensitivity and 69.1% specificity were observed. AGE levels can be used to cheaply, easily and non-invasively identify patients at risk of developing MAC.

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise. We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden. Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.

Is there a relationship between aortic valve degeneration and left ventricle function?

Is there a relationship between aortic valve degeneration and left ventricle function?

Role of lipoprotein(a) concentrations in bioprosthetic aortic valve degeneration

ObjectivesLipoprotein(a) (Lp(a)) is associated with an increased incidence of native aortic stenosis, which shares similar pathological mechanisms with bioprosthetic aortic valve (bAV) degeneration. However, evidence regarding the role of Lp(a)...

Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 × 10–16 and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci.uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.

Transcatheter Aortic Valve Implantation with the Portico Valve: 2-Year Outcomes of a Multicenter, Real-World Registry.

The self-expanding, resheathable, repositionable transcatheter aortic heart valve Portico is being used successfully for transcatheter aortic valve implantation procedures (TAVI) in patients with severe aortic stenosis. The aim of this study was to evaluate outcomes at 2 years after TAVI with the Portico valve. Multicenter registry of clinical, echocardiographic and survival data from consecutive patients treated with the Portico TAVI system (Abbott, Chicago, IL, USA) in three cath labs in Northern Greece and Epirus during 2017-2020. The primary end point was all-cause mortality at 24 months. Secondary end points included procedural outcomes (efficacy and safety) and echocardiographic measurements. A total of 90 patients (81 ± 6 years, 50% females, mean age 81 ± 6 years) were included in the registry. The indication for implantation was severe, symptomatic aortic stenosis (NYHA III, IV) in eighty-two (91.1%) and degeneration of a prosthetic aortic valve in eight (8.9%) patients. All patients were categorized as high surgical risk (mean Logistic Euroscore 25.9 ± 10, Euroscore II 7.7 ± 4.4 and STS score 10.8 ± 8.9). The procedure was performed transfemorally in all patients, under general anesthesia in 95.6%, under TOE guidance in 21.1%, with native valve predilatation in 46.7%, and the "resheath" option was used in 31.1% of the cases. The implantation was successful in 97.8% and there was a need for a second valve in 2.2% of the cases. Complications included permanent pacemaker implantation (16.7%), access cite complications (15.6%), arrythmias (23.3%), paravalvular leak (moderate 7.8%, severe 1.1%), acute kidney injury (7.8%), no strokes and one death during the procedure. Aortic valve peak velocity, peak and mean pressure gradients, were significantly reduced after the procedure. All-cause mortality at 1, 12 and 24 months was 4.4%, 6.7% and 7.8%, respectively. TAVI with the Portico system comprises an effective and safe solution for the management of severe, symptomatic aortic stenosis in high-risk surgical patients.

Impact of aortic valve stenosis on myocardial deformation in different left ventricular levels: A three-dimensional speckle tracking echocardiography study.

Global systolic left ventricular (LV) myocardial function progressively declines as degenerative aortic valve stenosis (AS) progresses. Whether this results in uniformly distributed deformation changes from base to apex has not been investigated. Eighty-five AS patients underwent three-dimensional (3D) echocardiography in this cross-sectional study. Patients were grouped by peak jet velocity into mild (n=32), moderate (n=31), and severe (n=22) AS. 3D speckle tracking derived strain, rotation, twist, and torsion were obtained to assess global LV function and myocardial function at the apical, mid, and basal levels. Global longitudinal strain (GLS) was lower in patients with severe AS (-16.1±2.4% in mild, -15.5±2.5% in moderate, and -13.5±3.0% in severe AS [all p<.01]). Peak basal and mid longitudinal strain (LS), basal rotation and twist from apical to basal level followed the same pattern, while peak apical LS was higher in moderate AS compared to severe AS (all p<.05). In multivariate analyses, lower GLS was particularly associated with male sex, higher body mass index and peak aortic jet velocity, lower basal LS with higher filling pressure (E/e') and LV mass, lower mid LS with higher RWT and presence of AS symptoms, and lower apical LS with male sex and higher systolic blood pressure, respectively (all p<.05). Using 3D speckle tracking echocardiography reveals regional and global changes in LV mechanics in AS related to the severity of AS, LV remodeling and presence of cardiovascular risk factors.

Degenerative calcific aortic valve stenosis: why not neglect vitamin D?

Degenerative calcific aortic valve stenosis: why not neglect vitamin D?

Association between remnant cholesterol and progression of bioprosthetic valve degeneration.

Remnant cholesterol (RC) seems associated with native aortic stenosis. Bioprosthetic valve degeneration may share similar lipid-mediated pathways with aortic stenosis. We aimed to investigate the association of RC with the progression of bioprosthetic aortic valve degeneration and ensuing clinical outcomes. We enrolled 203 patients with a median of 7.0 years (interquartile range: 5.1-9.2) after surgical aortic valve replacement. RC concentration was dichotomized by the top RC tertile (23.7 mg/dL). At 3-year follow-up, 121 patients underwent follow-up visit for the assessment of annualized change in aortic valve calcium density (AVCd). RC levels showed a curvilinear relationship with an annualized progression rate of AVCd, with increased progression rates when RC >23.7 mg/dL (P = 0.008). There were 99 deaths and 46 aortic valve re-interventions in 133 patients during a median clinical follow-up of 8.8 (8.7-9.6) years. RC >23.7 mg/dL was independently associated with mortality or re-intervention (hazard ratio: 1.98; 95% confidence interval: 1.31-2.99; P = 0.001). Elevated RC is independently associated with faster progression of bioprosthetic valve degeneration and increased risk of all-cause mortality or aortic valve re-intervention.

Risk factors for depresion and anxiety in the patient with aortic valve stenosis

Anxiety disorders and depression are common along with negative effects in different areas of the patient such as lower quality of life, lower adherence to treatment, negative perception of oneself along with underlying comorbidities and mortality, which is why these disorders are usually considered as symptoms and not as an independent factor that require greater detection, care and early treatment. Cardiovascular diseases are among the leading causes of mortality and morbidity in the world. Among them there is a subgroup of valvopathies which can occur in young patients (congenital alterations) and in elderly patients (called calcific or degenerative aortic valve stenosis) consisting of calcium crystal formation and lipid accumulation. These processes damage the valve generating aortic sclerosis characterized by thickening of the leaflets. Valvopathies are usually asymptomatic during the first years after their onset, and several modifiable and non-modifiable factors have been related to the progression of the disease. Psychological alterations can occur in these patients before, during and/or after discharge, generating mood disorders such as anxiety and depression, the frequency of which is unknown, which is why the general objective of the article is the importance of recognizing the symptomatology to favour prognosis through timely diagnosis to generate future interdisciplinary interventions and improve the quality of patients.

First-in-Human Multicenter Experience of the Newest Generation Supra-Annular Self-Expanding Evolut FX TAVR System

BackgroundThe latest-generation Evolut FX TAVR system (Medtronic) offers several potential design improvements over its predecessors, but early reported experience has been limited. ObjectivesThis study sought to report our multicenter, limited market release, first-in-human experience of transcatheter aortic valve replacement (TAVR) with the Evolut FX system and compare it with a single-center PRO+ (Medtronic) experience. MethodsFrom June 27 to September 16, 2022, 226 consecutive patients from 9 US centers underwent transfemoral TAVR with the Evolut FX system for native aortic stenosis (89.4%) or prosthetic valve degeneration (10.6%). Commissural alignment was defined as 0° to 30° between native and FX commissures. Patient, anatomical, and procedural characteristics were retrospectively reviewed, and 30-day clinical and echocardiographic outcomes per Valve Academic Research Consortium-3 definitions were reported. ResultsOf 226 patients, 34.1% were low risk, 4% had a bicuspid valve, and 11.5% had a horizontal root (≥60°). Direct Inline sheath (Medtronic) was used in 67.6% and Lunderquist stiff wire (Cook Medical) in 35.4% of cases. Optimal hat marker orientation during deployment was achieved in 98.4%, with commissural alignment in 96.5%. At 30 days, 14.3% mild, 0.9% moderate, and no severe paravalvular leak were observed. Compared with the Evolut PRO+ experience from 1 center, FX had a more symmetrical implantation with shallower depth at the left coronary cusp (P < 0.001), fewer device recaptures (26.1% vs 39.5%; P = 0.004), and improved commissural alignment (96.5% vs 80.2%; P < 0.001). ConclusionsThe Evolut FX system demonstrated favorable 30-day outcomes with a significant improvement over PRO+ in achieving commissural alignment, fewer device recaptures, and more symmetrical implantation. These features may benefit younger patients undergoing TAVR with the supra-annular, self-expanding valve, where lifetime management would be important.

The Sutureless Biological Bentall Procedure: A New Technique to Create a Modular Valve-Conduit Construct.

The Perceval sutureless valve (Corcym, Saluggia, Italy) has been effectively adopted by surgeons for the treatment of degenerative aortic valve stenosis. Its simplified true sutureless implantation technique has proven useful for minimally invasive cases, but the use of Perceval as part of more complex root replacement has not previously been described. We present a novel technical modification to the manufactured biologic Bentall, called the sutureless biological Bentall. This technique allows for a true modular valve-conduit construction that will simplify future reintervention.

Effect of Implantation of a new Domestic Prosthesis in the Aortic Position on the Quality of Life of Patients With Degenerative Aortic Stenose, Survival Assessment and Development of Complications 1 Year Post-Surgery.

Aim To evaluate quality of life (QoL), general survival, and development of complications in patents one year after surgical aortic valve (AV) replacement with a MedInzh-BIO xenopericardial carcass prosthesis.Material and methods Degenerative AV disease is one of the most common cardiovascular diseases that gives place only to ischemic heart disease. Surgical correction of the AV defect should be aimed not only at hemodynamic outcomes but also at improvement of QoL. This study included 91 patients (48 women and 43 men), who were implanted with a MedInzh-BIO biological xenopericardial prosthesis in aortic position from January 2017 through March 2020. Mean age of patients was 69.96±4.4 years. QoL was evaluated with a standard SF-36 questionnaire. Also, survival and complications were analyzed one year after surgery.Results Data analysis before and one year after surgery showed a significant improvement of QoL. Postoperative one-year survival was 95.4 %, and major valve-associated complications were absent in 94.5% of cases. During one year, four patients died after 1, 6, 8, and 10 months of follow-up, respectively.Conclusion The improvement of QoL following the AV replacement with a novel xenopericardial carcass prosthesis with the "easy change" system indicates the clinical and functional effectiveness of the used method. The results of the study demonstrated improvements of both the physical health component and the subjective emotional assessment. Postoperative one-year survival was 95.4 %, and major valve-associated complications were absent in 94.5% of cases.

High-Throughput Metabolomics Applications in Pathogenesis and Diagnosis of Valvular Heart Disease.

High-throughput metabolomics techniques are a useful tool to understand many disease conditions including cardiovascular disease such as valvular heart disease(s) (VHD). VHD involves damage to heart valves, mostly presenting as stenosis, regurgitation or prolapse and can be classified into degenerative, rheumatic, congenital, or prosthetic valve disease. Gaps remain in our understanding of the pathogenesis of the common VHD. It is now fitting to place into perspective the contribution of metabolomics in the mechanism of development, diagnosis, and prognosis of VHD. A structured search for metabolomics studies centred on human VHD was undertaken. Biomarkers associated with the pathogenesis of bicuspid aortic valve disease, mitral valve disease, rheumatic heart disease, and degenerative aortic valve stenosis are reviewed and discussed. In addition, metabolic biomarkers reported to prognosticate patient outcomes of post-valve repair or replacement are highlighted. Finally, we also review the pitfalls and limitations to consider when designing metabolomics studies, especially from a clinician's viewpoint. In the future, reliable and simple metabolic biomarker(s) may supplement the existing diagnostic tools in the early diagnosis of VHD.