Aortic Valve Stenosis Patients Research Articles

Improvement in Left Ventricular Function of the Resected Myocardium after Septal Myectomy in Patients with Aortic Valve Replacement

Background: Some surgeons have previously advocated for a more aggressive concomitant septal myectomy to address left ventricular outflow tract obstruction; however, concerns about the surgical complications of post-septal myectomy remain. Here, we aimed to assess the clinical, echocardiographic, and pathological findings following concomitant septal myectomy with surgical aortic valve replacement. Methods: We reviewed 21 patients who underwent surgical aortic valve replacement and concomitant septal myectomy from April 2014 to September 2019. The global and regional left ventricular ejection fraction changes between the perioperative periods were analyzed using two-dimensional speckle-tracking echocardiography. The resected myocardium was pathologically assessed. Results: No operative mortality was observed during the study period. Transthoracic echocardiography showed no significant differences in preoperative and postoperative left ventricular ejection fraction (68.1 ± 9.9% vs. 68.6 ± 6.0%, p = 0.82) or interventricular septum thickness (11.9 ± 1.4 mm vs. 11.5 ± 1.5 mm, p = 0.23). Interventricular septum thickness at the end-systolic phase, which is the maximum septal wall thickness, was significantly reduced postoperatively (27.7 ± 9.3 mm vs. 22.6 ± 5.5 mm, p < 0.05). The basal, mid, and apical septal areas improved with septal myectomy by 80%, 230%, and 27%, respectively, compared to perioperative echocardiography (basal septal, 80 ± 23%; mid septal, 230 ± 830%; apical septal, 27 ± 350%). Pathological examination of the resected myocardium revealed marked endocardial thickness (mean, 914 µm) with focal fibrosis. Conclusions: In aortic valve stenosis patients with septal hypertrophy, concomitant septal myectomy with surgical aortic valve replacement improved regional myocardial function and eliminated left ventricular outflow tract obstruction by removing thickened endocardium and prominent fibrosis.

Quantification of functional hemodynamics in aortic valve disease using cardiac computed tomography angiography

Background and Objective:Cardiac computed tomography angiography (CTA) is the preferred modality for preoperative planning in aortic valve stenosis. However, it cannot provide essential functional hemodynamic data, specifically the mean transvalvular pressure gradient (MPG). This study aims to introduce a computational fluid dynamics (CFD) approach for MPG quantification using cardiac CTA, enhancing its diagnostic value. Methods:Twenty patients underwent echocardiography, cardiac CTA, and invasive catheterization for pressure measurements. Cardiac CTA employed retrospective electrocardiographic gating to capture multi-phase data throughout the cardiac cycle. We segmented the region of interest based on mid-systolic phase cardiac CTA images. Then, we computed the average flow velocity into the aorta as the inlet boundary condition, using variations in end-diastolic and end-systolic left ventricular volume. Finally, we conducted CFD simulations using a steady-state model to obtain pressure distribution within the computational domain, allowing for the derivation of MPG. Results:The mean value of MPG, measured via invasive catheterization (MPGInv), echocardiography (MPGEcho), and cardiac CTA (MPGCT), were 51.3 ± 28.4 mmHg, 44.8 ± 19.5 mmHg, and 55.8 ± 25.6 mmHg, respectively. In comparison to MPGInv, MPGCT exhibited a higher correlation of 0.91, surpassing that of MPGEcho, which was 0.82. Moreover, the limits of agreement for MPGCT ranged from −27.7 to 18.7, outperforming MPGEcho, which ranged from −40.1 to 18.0. Conclusions:The proposed method based on cardiac CTA enables the evaluation of MPG for aortic valve stenosis patients. In future clinical practice, a single cardiac CTA examination can comprehensively assess both the anatomical and functional hemodynamic aspects of aortic valve disease.

The role of the vascular surgeon in transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) has become the standard treatment for severe aortic valve stenosis in patients at increased surgical risk. Percutaneous transfemoral (TF) is the access of choice due to its reduced invasiveness and perioperative morbidity/mortality compared with the trans-axillary, aortic, and apical routes. On the other hand, vascular access complications (VACs) of the TF access are associated with prolonged hospitalization, 30-day, and 1-year mortality. In addition, the concomitance of peripheral arterial disease may require associated endovascular management. A multidisciplinary team with Interventional Cardiologists and Vascular Surgeons may minimize the rate of VACs in patients with challenging femoral-iliac access or concomitant disease of other vascular districts, thus optimizing the outcome of TF-TAVI. The aim of this study was to evaluate the role of Vascular Surgeons in TF TAVI procedures. We conducted a retrospective single-center review of all TF-TAVI procedures assisted by Vascular Surgeons between January 2016 and December 2020 in a high-volume tertiary hospital. Pre, intra, and postoperative data were analyzed by a dedicated group of Interventional Cardiologists and Vascular Surgeons. VACs were defined according with the Valve Academic Research Consortium (VARC) three guidelines. The outcomes of TF-TAVI procedures with Vascular Surgeons involvement were assessed as study's endpoints. Overall, 937 TAVI procedures were performed with a TF approach ranging between 78% (2016) and 98% (2020). Vascular Surgeons were involved in 67 (7%) procedures with the following indications: concomitant abdominal aortic aneurysm (EVAR + TAVI) - 3 (4%), carotid stenosis (TAVI + CAS) - 2 (3%), hostile femoral/iliac access, or VACs - 62 (93%). Balloon angioplasty of iliac artery pre-TAVI implantation was performed in 51 cases (conventional PTA: 38/51%-75%; conventional PTA + intravascular lithotripsy: 13/51%-25%; stenting: 5/51%-10%). TAVI procedure was successfully completed by percutaneous TF approach in all 62 cases with challenging femoral/iliac access. VACs necessitating interventions were 18/937 (2%) cases, localized to the common femoral or common/external iliac artery in 15/18 (83%) and 3/18 (17%) cases, respectively. They were managed by surgical or endovascular maneuvers in 3/18 (17%) and 15/18 (83%) cases, respectively. Fifteen/18 (83%) VACs were treated during the index procedure. There was no procedure-related mortality or 30-day readmission. In our experience, Vascular Surgeon assistance in TAVI procedures was not infrequent and allowed safe and effective device introduction through challenging TF access. Similarly, the concomitant significant disease of other vascular districts could be safely addressed, potentially reducing postoperative related mortality and morbidity. The implementation of multidisciplinary team with interventional cardiologists and vascular surgeons should be encouraged whenever possible.

Low-flow in aortic valve stenosis patients with reduced ejection fraction does not depend on left ventricular function.

Patients with severe aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF) can be distinguished into high- (HG) and low-gradient (LG) subgroups. However, less is known about their characteristics and underlying (pathophysiological) hemodynamic mechanisms. 98 AS patients with reduced LVEF were included. Subgroup characteristics were analyzed by a multimodal approach using clinical and histological data, next-generation sequencing (NGS) and applying echocardiography as well as cardiovascular magnetic resonance (CMR) imaging. Biopsy samples were analyzed with respect to fibrosis and mRNA expression profiles. 40 patients were classified as HG-AS and 58 patients as LG-AS. Severity of AS was comparable between the subgroups. Comparison of both subgroups revealed no differences in LVEF (p = 0.1), LV mass (p = 0.6) or end-diastolic LV diameter (p = 0.12). Neither histological (HG: 23.2% vs. LG: 25.6%, p = 0.73) and circulating biomarker-based assessment (HG: 2.6 ± 2.2% vs. LG: 3.2 ± 3.1%; p = 0.46) of myocardial fibrosis nor global gene expression patterns differed between subgroups. Mitral regurgitation (MR), atrial fibrillation (AF) and impaired right ventricular function (MR: HG: 8% vs. LG: 24%; p < 0.001; AF: HG: 30% vs. LG: 51.7%; p = 0.03; RVSVi: HG 36.7 vs. LG 31.1ml/m2, p = 0.045; TAPSE: HG 20.2 vs. LG 17.3mm, p = 0.002) were more frequent in LG-AS patients compared to HG-AS. These pathologies could explain the higher mortality of LG vs. HG-AS patients. In patients with low-flow severe aortic stenosis, low transaortic gradient and cardiac output are not primarily due to LV dysfunction or global changes in gene expression, but may be attributed to other additional cardiac pathologies like mitral regurgitation, atrial fibrillation or right ventricular dysfunction. These factors should also be considered during planning of aortic valve replacement.

Balloon-expandable transcatheter heart valves for treatment of aortic valve stenosis in patients with large aortic annuli: Evaluation of deployment balloon overfilling strategies.

Transcatheter aortic valve implantation (TAVI) using balloon-expandable (BE) transcatheter heart valves (THV) in aortic annuli above 29 mm includes particular procedural steps, mainly involving overfilling of the deployment balloon. Data on overfilling strategies in clinical daily practice is scarce. We herein aimed for a retrospective description of utilized overfilling strategies in those patients. Between January 2016 and December 2022, 45 patients (100% male, 76.9 ± 6.1 years) received TAVI in aortic annuli above 29 mm using a BE THV. Overfilling volumina of the deployment balloon were left to operators' discretion. Clinical and multislice computed tomography data were retrospectively collected. Clinical endpoints were adjudicated in accordance with the updated standardized VARC-3 definitions. Profound overfilling (+4/5 mL) was used in patients with a mild calcium burden (˂750 mm³) even in aortic annuli of 29.0-30.0 mm. Nominal/slight overfilling (+1 mL) was used in aortic annuli up to 32.5 mm but an intermediate to severe calcific burden (>750-3200 mm³). Accordingly, a low calcification group (˂750 mm³, n = 17) compared to a significant calcification group (≥750 mm³, n = 28), presented with higher overfilling volumina (2.1 ± 1.4 vs. 0.8 ± 1.0; p ˂ 0.001), although aortic annulus diameter was not different (29.8 ± 0.8 vs. 29.9 ± 0.9 mm; p = 0.7). All-cause 30-day mortality was 0%. Device success was 97.8%. Transvalvular mean pressure gradient at discharge was 9.5 ± 3.6 mmHg. No case of PVL >mild was documented. Extent of overfilling of the deployment balloon largely depends on calcification burden in addition to aortic annulus diameter with significant and profound overfilling particularly in patients with a calcification burden of the aortic valve complex ˂750 mm³.

Myocardial work index and myofilament calcium sensitivity: possible hand in hand markers of contractility in aortic valve stenosis patients - a translational study

Abstract Background In aortic valve stenosis, conventional echocardiographic parameters, such as ejection fraction (EF), are heavily influenced by the increased afterload caused by the valvular disease. Myocardial work index (GWI) quantifies myocardial deformation depending on the momentary LV pressure, potentially serving as a marker of LV contractility independent of loading conditions. Similarly, myofilament Ca2+ sensitivity (pCa50) followed the alterations of LV contractility in a rat model of pressure overload-induced heart failure. Therefore, GWI and pCa50 may also show correlation, as both can be reliable measures of contractility in diseases of chronically elevated LV afterload. Purpose Accordingly, our first aim was to assess the association of pCa50 and GWI in a rat model of pressure overload-induced heart failure and sham operated animals. We also aimed to evaluate the changes in GWI after myocardial Ca2+ sensitizing with levosimendan in aortic valve stenosis patients. Methods Firstly, on the thoracic aortic banded (n=2) and sham operated (n=3) rats speckle-tracking echocardiography and invasive LV pressure measurements were performed to calculate GWI. Using single permeabilized cardiomyocytes, pCa50 was calculated by myofilament force measurement. Secondly, to test our hypothesis in a clinical setting, 23 severe aortic valve stenosis patients (age 76±9 years, 39% female) were enrolled who received levosimendan therapy. Conventional and advanced echocardiographic measurements were performed before and after a 24-hour intravenous loading dose. We determined global longitudinal strain by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean transaortic gradient, we quantified non-invasive global myocardial work index (GWI). Results In the animal study, GWI and pCa50 strongly correlated in the rats (r=0.942; p=0.017). In the clinical study, patients with a baseline EF &amp;lt;35% (n=12) had significantly increased GWI after the levosimendan therapy (533±347 vs. 660±419 mmHg%; p=0.004), while those who initially had an EF &amp;gt;35% (n=11) did not show any change (998±342 vs. 1003±275 mmHg%; p= 0.788). Also, the pre-levosimendan GWI showed a strong inverse correlation with the relative GWI change after the loading dose (r=-0.708; p=0.003). Conclusions We showed in an experimental setting, that GWI and pCa50 correlated in a rat model of pressure overload-induced heart failure and in sham operated controls. In the clinical setting, patients with severely decreased baseline EF and GWI benefited more from the Ca2+ sensitizing therapy, having better LV function after it, while those with better baseline function did not show improvement. Therefore, patients with worse baseline GWI initially might have had decreased Ca2+ sensitivity, which implies a possible correlation between GWI and pCa50 in patients with aortic valve stenosis, resembling the experimental findings.Correlation of pCa50 - GWICorrelation of GWI - relative GWI change

Enhanced expression of iNOS is associated with aortic valve stenosis in patients with bicuspid aortic valve

Abstract Background A congenital bicuspid aortic valve (BAV) is one of the most common congenital cardiac abnormalities, with a prevalence estimated between 0.5% and 2%. Aortic valve stenosis (AS) is the most common complication in patients with BAV. The mechanisms responsible for the rapid progression of AS in patients with BAV relative to those with a tricuspid aortic valve (TAV) are unknown. A previous study showed that the pathogenesis of AS in patients with BAV is associated with a more aggressive inflammatory process, with increased macrophage infiltration and neo-vascularization when compared with that seen in patients with TAV. A considerable number of human diseases have an inflammatory component, and a key mediator of immune activation and inflammation is inducible nitric oxide synthase (iNOS). Overexpressed iNOS has been implicated in the pathogenesis of numerous conditions, including coronary plaque destabilization. To elucidate the role of iNOS in the aortic valve of patients with AS, we carried out an immunohistochemical study of the presence of iNOS in aortic valve specimens from patients with AS with either TAV or BAV. Methods Frozen aortic valve samples were obtained surgically from patients with AS with TAV (n=34) or BAV (n=34), and stained with antibodies against macrophages, microvessels, iNOS and 4-hydroxy-2-nonenal (4-HNE), an index of lipid peroxidation. The immunoreactivity of macrophages, microvessels, iNOS and 4-HNE was quantified using computer-aided polarimetry. Double immunostaining was also performed to identify cell types that stained positive for iNOS. Results Quantitative analysis demonstrated that macrophage-, iNOS-, and 4-HNE-positive areas, as well as the number of microvessels, were significantly higher in patients with AS with BAV than with TAV (macrophages, P&amp;lt;0.001; microvessels, P&amp;lt;0.05; 4-HNE, P&amp;lt;0.05; iNOS, P&amp;lt;0.001). The iNOS-positive area was positively correlated with the 4-HNE-positive area (R=0.43, P&amp;lt;0.0001). Double immunostaining for both iNOS and macrophages identified iNOS-positive cells as macrophages. Conclusions These findings suggest that accumulation of iNOS in macrophages may increase oxidative stress and contribute to the rapid progression of AS in patients with BAV.

Prognostic value of coronary microvascular dysfunction in patients with aortic stenosis and nonobstructed coronary arteries.

Patients with aortic valve stenosis have been postulated to have coronary microvascular dysfunction (CMD) contributing to the clinical symptoms and adverse outcomes. The coronary angiography (CAG)-derived index of microcirculatory resistance (caIMR) is proposed as a novel, less invasive and pressure-wire-free index to assess CMD. This study aimed to quantify CMD assessed by caIMR and investigate its prognostic impact in patients with aortic valve stenosis. This study included 77 moderate or severe aortic valve stenosis patients with no obstructive coronary disease (defined as having no stenosis more than 50% in diameter) who underwent caIMR measurement. CMD was defined by caIMR at least 25. Major adverse cardiovascular events (MACE) were the clinical outcomes during the median 40 months of follow-up. The incidence of CMD was 47.7%. Seventeen MACE occurred during the follow-up duration. CMD was associated with an increased risk of MACE (log-rank P < 0.001) and an independent predictor of clinical outcomes [hazard ratio 5.467, 95% confidence interval (CI) 1.393-21.458; P = 0.015]. The receiver-operating characteristic (ROC) curve analysis demonstrated that caIMR could provide a significant predictive value for MACE in aortic valve stenosis patients (AUC 0.785, 95% CI 0.609-0.961, P < 0.001). In addition, the risk of MACE was higher in CMD patients with severe aortic valve stenosis (log-rank P < 0.001) and no aortic valve replacement (log-rank P = 0.003) than in other groups. Aortic valve stenosis patients demonstrated markedly impaired caIMR. CMD assessed by caIMR increases the risk of MACE and is an independent predictor of adverse outcomes in aortic valve stenosis patients. This finding suggests that using caIMR in the clinical assessment may help identify high-risk groups and stimulate earlier intervention.

Short-Term Outcomes Among Aortic Valve Stenosis Patients Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention

Short-Term Outcomes Among Aortic Valve Stenosis Patients Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention

Single-cell transcriptomics reveals cellular heterogeneity and macrophage-to-mesenchymal transition in bicuspid calcific aortic valve disease

BackgroundBicuspid aortic valve (BAV) is the most prevalent congenital valvular heart defect, and around 50% of severe isolated calcific aortic valve disease (CAVD) cases are associated with BAV. Although previous studies have demonstrated the cellular heterogeneity of aortic valves, the cellular composition of specific BAV at the single-cell level remains unclear.MethodsFour BAV specimens from aortic valve stenosis patients were collected to conduct single-cell RNA sequencing (scRNA-seq). In vitro experiments were performed to further validate some phenotypes.ResultsThe heterogeneity of stromal cells and immune cells were revealed based on comprehensive analysis. We identified twelve subclusters of VICs, four subclusters of ECs, six subclusters of lymphocytes, six subclusters of monocytic cells and one cluster of mast cells. Based on the detailed cell atlas, we constructed a cellular interaction network. Several novel cell types were identified, and we provided evidence for established mechanisms on valvular calcification. Furthermore, when exploring the monocytic lineage, a special population, macrophage derived stromal cells (MDSC), was revealed to be originated from MRC1+ (CD206) macrophages (Macrophage-to-Mesenchymal transition, MMT). FOXC1 and PI3K-AKT pathway were identified as potential regulators of MMT through scRNA analysis and in vitro experiments.ConclusionsWith an unbiased scRNA-seq approach, we identified a full spectrum of cell populations and a cellular interaction network in stenotic BAVs, which may provide insights for further research on CAVD. Notably, the exploration on mechanism of MMT might provide potential therapeutic targets for bicuspid CAVD.

Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients.

Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load-independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention. To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR). We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient. All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior-TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post-TAVR benefit. The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment.

CRT-700.34 Short-Term Outcomes Among Aortic Valve Stenosis Patients Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention

CRT-700.34 Short-Term Outcomes Among Aortic Valve Stenosis Patients Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention

Transcatheter Aortic Valve Replacement for Bicuspid vs. Tricuspid Aortic Stenosis among Patients at Low Surgical Risk in China: From the Multicenter National NTCVR Database.

This study aims to compare the outcomes of transcatheter aortic valve replacement (TAVR) with self-expandable valves for bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) stenosis patients who are at low surgical risk. Participants were enrolled from 36 centers in China between January 2017 and December 2021. The primary endpoint event was all-cause mortality and all stroke at 30 days. Among 389 patients at low surgical risk that underwent TAVR, 229 patients were BAV stenosis (mean age, 72.9 years; 65.1% men). There was no significant difference in the rate of all-cause death between two populations at 30 days. However, the rate of all stroke was significantly higher in the BAV group at 30 days (3.3% vs. 0%; odds ratio (OR), 0.97 (95% confidence interval (CI), 0.94 to 0.99); p = 0.044). By multivariate logistic regression analysis, trans-carotid access was associated with a higher all stroke rate at 30 days (OR, 29.20 (95% CI, 3.97 to 215.1); p = 0.001). In this national registry-based study, patients treated for BAV vs. TAV stenosis had no significant difference in all-cause mortality at 30 days, but trans-carotid access was associated with a higher all stroke rate after TAVR at 30 days.

Registry of aortic valve stenosis patients in delta region in Egypt

Background: The most widespread valvular heart disease in industrialised nations is aortic stenosis (AS), and its rate rises with age. In relation to the present causes, the purpose of this paper was to characterise the clinical features of AS patients in the Delta area of Egypt, diagnostic and treatment strategies to improve the care of those patients. Methods: This prospective, observational, multicenter registry research involved 700 patients with prosthetic aortic valves and clinical criteria for mild, moderate, and severe AS. Aortic-valve gradients of less than 25 mmHg were considered mild, 25–40 mmHg were judged moderate, and greater than 1 cm2 was deemed severe based on European Society of Cardiology (ESC) standards. Results: Regarding age 43% were males and 57% were females, the severity 12% moderate, and severe in 18%, 4% participants had prosthetic valve. Echocardiography showed that 41% of patients had left ventricular hypertrophy. The ejection fraction (EF) ranged from 36 to 70 %, for Electrocardiogram, 68% had sinus rhythm, 18% had Atrial fibrillation, 10% had left Bundle branch block (BBB), and 4% had pathological Q wave, type of treatment was medical in 80% participants, and surgical in 13%, and Transcatheter aortic valve replacement (TAVI) in 1%, 2% participants refused surgery and 4% were medically non-fit for surgery. Conclusions: No pharmaceutical treatment is presently effective in minimising the development of AS, and patient-education efforts will see a spike in the rate of AS in the population who are 50 years old and older, in both sexes, TAVI and Screening programs should be initiated among AS patients.

Orengedokuto inhibits TNF-α-induced HAVIC calcification obtained from calcific aortic valve stenosis patients

Orengedokuto inhibits TNF-α-induced HAVIC calcification obtained from calcific aortic valve stenosis patients

Novel peripheral blood immune cell populations correlate with disease progression and reveal systemic interactions in severe aortic valve stenosis patients

Abstract Background Osteoblastic differentiation is the key driver phenomenon underlying degenerative aortic valve stenosis (AS). It is characterized by a complex cellular interplay and infiltration by circulating immune cells. Moreover, AS demonstrates a diverse natural course, which is understudied. Purpose We sought to investigate the presence of AS clinical progression subphenotypes in the context of “AthenaValve” trial (NCT04312139). Methods Consecutive patients with severe AS undergoing TAVI or SAVR with complete clinical data, echocardiographic history (≥3 past years, corresponding from moderate to severe AS), along with matched healthy volunteers, were included. The median transaortic Vmax increase/month (Vi/m) was calculated and cluster analysis was used to reveal AS progression subgroups. Whole blood peripheral mononuclear cells (PBMCs) were isolated with density gradient centrifugation and cryopreserved into FBS-10% DMSO. PBMC populations were investigated with mass cytometry (CyTOF, Helios, Fluidigm) using a 30-marker antibody panel (Direct Immune Profiling Assay, Fluidigm) and analyzed with Flowjo and Cytobank software. Results A total of 67 patients fulfilling criteria were included (mean age 77.2±10 years, 61.2% males). Two-step cluster algorithm identified 2 clusters of AS progression: C1: 80%, mean Vi/m = 0.03±0.01 vs C2: 20%, Vi/m = 0.07±0.1 m/s/month, average silhouette = 0.7. Mean time to progression to severe AS differed significantly: C1: 59.5 (48.9,70.1) vs C2: 40.2 (29.2, 51.2) months, log rank p=0.05. Among those, 20 patients (C1: 10, C2: 10) and 10 healthy volunteers were included in CyTOF. Demographics, atherosclerotic clinical factors and renal function did not differ among patients-volunteers and C1-C2 groups. B cells, B-memory, B-naïve and pDendritic cells discriminated patients from healthy volunteers: ROC curve (AUC: 0.885, p=0.001), (0.913, p&amp;lt;0.001), (0.770, p=0.018), (0.282, p=0.056), profile (%): (5.3±3 vs 10.2±4), (0.86±0.4 vs 2.6±2), (4.4±3 vs 7.6±4), and (0.48±0.2 vs 0.3±0.1), respectively (mean live cells analyzed: 284028.8±52213.8). pDendritic cells and CD4-Th17-like cells discriminated C1 from C2 patients: ROC curve AUC: (0.804, p=0.005) and (0.268, p=0.031), profile (%): (0.6±0.2 vs 0.3±0.2) and (0.9±0.5 vs 2.6±0.9), respectively). Conclusions Aortic valve stenosis patients demonstrate two distinct phenotypes of disease progression from moderate to severe stage. Patients demonstrate reduced circulating B-cells and increased plasmatocytoid dendritic cells. The rapid progression subgroup of patients demonstrates reduced pDendritic and increased CD4-Th17-like cells. Further works are needed to expand and validate these results. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Co-Funded by Hellenic Ministry of Development and European Regional Development Fund in the context of an open call of “EATRIS-GR project: Infrastructure for preclinical and early-phase clinical development of drugs, therapeutics, and biomedical devices”

Incidence, Outcomes and Predictors of Aortic Regurgitation After Transcatheter Aortic Valve Replacement in Al Azhar University Hospitals and National Heart Institute, Egypt

Background: Aortic regurgitation (AR), which has ill-defined predictors and an unknown long-term influence on outcomes, is a significant transcatheter aortic valve replacement (TAVR) constraint. Objective: this research aimed to assess the prevalence, identify predictors, and evaluate the outcomes of aortic regurgitation following trans catheter aortic valve implantation (TAVI). 1. To calculate the prevalence of aortic regurgitation in elderly patients receiving trans catheter aortic valve implantation who have severe symptomatic aortic stenosis. 2. To determine aortic regurgitation risk factors after trans catheter aortic valve implantation. Methods: From November 2017 to November 2020, this prospective observational study was done in the National Heart Institute on severe aortic valve stenosis patients above 65 years who were candidates for aortic valve replacement from the outpatient department. Results: LVEF significantly improved. Compared to before TAVI (55.08 ± 9.71), LVEF elevated to 58.9 ± 8.8 (P&lt;0.001). Twenty-five patients (83.3%) showed class III/IV, four patients (13.3%) showed class II, and one patient (3.3%) showed class I before TAVI. While after TAVI, three patients (10%) only showed NYHA class III/IV, six patients (20 %) in class II, and 21 patients (70%) improved to be in class I. The left ventricular mass index mean was 158 ±32.37 before TAVI and 133.50 ±21.96 after TAVI (p&lt;0.001). Compared to before TAVI (0.75 ± 0.2), mean aortic valve area was improved to 2.0 ± 0.2 following TAVI (P&lt;0.001). A significant reduction in the mean pressure gradient from 47 ± 11.08 mmHg across the native valve prior to TAVI to 10.28 ± 3.21 mmHg across the prosthetic valve following TAVI (P &lt;0.001). Expert commentary: The clinical and results of TAVR devices were clearly outlined in literature study. The study showed a high incidence of pacemaker implantation with Core valve and aortic regurgitation. This information strongly supports the need for a randomized trial with sufficient power to compare the most recent self-expandable valve generation to balloon expandable valves. In the 2019 PARTNER 3 prospective randomized trial, it was discovered that, when compared to surgical management, low-risk patients (defined as STS 4%) had a lower risk of the composite outcome of stroke, death, and rehospitalization at 1 year. Additionally, it was shown that TAVR had a lower risk of stroke and required less time in the hospital (3 days as opposed to 7, P0.001) than surgery [1]. In addition, despite an elevated permanent pacemaker implantation rate, the 2019 Medtronic Evolut Transcatheter Aortic Valve Replacement revealed no inferiority for composite all-cause stroke and death, as well as a statistically significant decrease in the rates of life-threatening bleeding, acute kidney injury and atrial fibrillation, compared with SAVR at 30 days following the procedure [2]. Conclusion: According to the study in high-risk patients with severe symptomatic aortic stenosis, TAVI is alternative, viable, safe, and successful therapy compared to traditional open-heart surgery.

The role of neutrophil elastase in aortic valve calcification

BackgroundCalcific aortic valve disease (CAVD) is the most commonly valvular disease in the western countries initiated by inflammation and abnormal calcium deposition. Currently, there is no clinical drug for CAVD. Neutrophil elastase (NE) plays a causal role in inflammation and participates actively in cardiovascular diseases. However, the effect of NE on valve calcification remains unclear. So we next explore whether it is involved in valve calcification and the molecular mechanisms involved.MethodsNE expression and activity in calcific aortic valve stenosis (CAVD) patients (n = 58) and healthy patients (n = 30) were measured by enzyme-linked immunosorbent assay (ELISA), western blot and immunohistochemistry (IHC). Porcine aortic valve interstitial cells (pVICs) were isolated and used in vitro expriments. The effects of NE on pVICs inflammation, apoptosis and calcification were detected by TUNEL assay, MTT assay, reverse transcription polymerase chain reaction (RT-PCR) and western blot. The effects of NE knockdown and NE activity inhibitor Alvelestat on pVICs inflammation, apoptosis and calcification under osteogenic medium induction were also detected by RT-PCR, western blot, alkaline phosphatase staining and alizarin red staining. Changes of Intracellular signaling pathways after NE treatment were measured by western blot. Apolipoprotein E−/− (APOE−/−) mice were employed in this study to establish the important role of Alvelestat in valve calcification. HE was used to detected the thickness of valve. IHC was used to detected the NE and α-SMA expression in APOE−/− mice. Echocardiography was employed to assess the heat function of APOE−/− mice.ResultsThe level and activity of NE were evaluated in patients with CAVD and calcified valve tissues. NE promoted inflammation, apoptosis and phenotype transition in pVICs in the presence or absence of osteogenic medium. Under osteogenic medium induction, NE silencing or NE inhibitor Alvelestat both suppressed the osteogenic differentiation of pVICs. Mechanically, NE played its role in promoting osteogenic differentiation of pVICs by activating the NF-κB and AKT signaling pathway. Alvelestat alleviated valve thickening and decreased the expression of NE and α-SMA in western diet-induced APOE−/− mice. Alvelestat also reduced NE activity and partially improved the heart function of APOE−/−mice.ConclusionsCollectively, NE is highly involved in the pathogenesis of valve calcification. Targeting NE such as Alvelestat may be a potential treatment for CAVD.

Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Systematic Review of Non-Invasive Ways of Risk Stratification, Especially in Patients Undergoing Transcatheter Aortic Valve Replacement.

Patients with severe aortic valve stenosis and concomitant pulmonary hypertension show a significantly reduced survival prognosis. Right heart catheterization as a preoperative diagnostic tool to determine pulmonary hypertension has been largely abandoned in recent years in favor of echocardiographic criteria. Clinically, determination of echocardiographically estimated systolic pulmonary artery pressure falls far short of invasive right heart catheterization data in terms of accuracy. The aim of the present systematic review was to highlight noninvasive possibilities for the detection of pulmonary hypertension in patients with severe aortic valve stenosis, with a special focus on cardiovascular biomarkers. A total of 525 publications regarding echocardiography, cardiovascular imaging and biomarkers related to severe aortic valve stenosis and pulmonary hypertension were analyzed in a systematic database analysis using PubMed Central®. Finally, 39 publications were included in the following review. It was shown that the current scientific data situation, especially regarding cardiovascular biomarkers as non-invasive diagnostic tools for the determination of pulmonary hypertension in severe aortic valve stenosis patients, is poor. Thus, there is a great scientific potential to combine different biomarkers (biomarker scores) in a non-invasive way to determine the presence or absence of PH.

Network modeling predicts personalized gene expression and drug responses in valve myofibroblasts cultured with patient sera

Aortic valve stenosis (AVS) patients experience pathogenic valve leaflet stiffening due to excessive extracellular matrix (ECM) remodeling. Numerous microenvironmental cues influence pathogenic expression of ECM remodeling genes in tissue-resident valvular myofibroblasts, and the regulation of complex myofibroblast signaling networks depends on patient-specific extracellular factors. Here, we combined a manually curated myofibroblast signaling network with a data-driven transcription factor network to predict patient-specific myofibroblast gene expression signatures and drug responses. Using transcriptomic data from myofibroblasts cultured with AVS patient sera, we produced a large-scale, logic-gated differential equation model in which 11 biochemical and biomechanical signals were transduced via a network of 334 signaling and transcription reactions to accurately predict the expression of 27 fibrosis-related genes. Correlations were found between personalized model-predicted gene expression and AVS patient echocardiography data, suggesting links between fibrosis-related signaling and patient-specific AVS severity. Further, global network perturbation analyses revealed signaling molecules with the most influence over network-wide activity, including endothelin 1 (ET1), interleukin 6 (IL6), and transforming growth factor β (TGFβ), along with downstream mediators c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription (STAT), and reactive oxygen species (ROS). Lastly, we performed virtual drug screening to identify patient-specific drug responses, which were experimentally validated via fibrotic gene expression measurements in valvular interstitial cells cultured with AVS patient sera and treated with or without bosentan-a clinically approved ET1 receptor inhibitor. In sum, our work advances the ability of computational approaches to provide a mechanistic basis for clinical decisions including patient stratification and personalized drug screening.