The aim of this study was to evaluate the outcomes of transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BiAV) stenosis using a mechanically expanded Lotus™ device. The prior experience with first-generation devices showed disappointing results mainly due to increased prevalence of aortic regurgitation (AR) that exceeded those observed in tricuspid stenosis.

Right ventricular (RV) function is a major determinant of clinical outcome, but its function indices have not been studied well in surgery for rheumatic valvular heart disease. The aim of this study was to determine the correlation of tricuspid annular plane systolic excursion (TAPSE) with outcome of rheumatic heart valve surgery.

This study was conducted to compare the outcomes of prosthetic ring versus autologous pericardial strip for the treatment of functional tricuspid regurgitation during left-sided valve surgery by minimally invasive approach.

Objective: To determine the association between spectral Doppler cardiac activity in the lower limb veins and echocardiographic findings in patients with tricuspid regurgitation. Material and methods: A cross-sectional analysis was performed in the Gilani Ultrasound Center over a period of 13 months. The total study sample comprised 400 subjects. All individuals referred for abdominal ultrasound having cardiac activities in external iliac vein, popliteal and posterior tibial vein, individuals having normal venous Doppler ultrasound, both genders and all ages, were included, and unwilling and non-cooperative patients were excluded from the study. Results: Out of 400 individuals, 200 showed cardiac activity in the lower limb veins on Doppler vascular ultrasound, while 200 did not show cardiac activity. On echocardiography, 204 individuals were diagnosed with tricuspid regurgitation, and 196 individuals had a competent tricuspid valve. According to the independent sample t-test the mean difference in the posterior tibial vein was 25.54 (95% CI: 24.09; 26.98), while the mean difference in the iliac vein was 2.34 (95% CI: 0.64; 4.03) among normal and tricuspid regurgitation. Conclusion: A correlation was found between the cardiac activities in the lower limb veins and tricuspid regurgitation. Objective: To determine the association between spectral Doppler cardiac activity in the lower limb veins and echocardiographic findings in patients with tricuspid regurgitation. Material and methods: A cross-sectional analysis was performed in the Gilani Ultrasound Center over a period of 13 months. The total study sample comprised 400 subjects. All individuals referred for abdominal ultrasound having cardiac activities in external iliac vein, popliteal and posterior tibial vein, individuals having normal venous Doppler ultrasound, both genders and all ages, were included, and unwilling and non-cooperative patients were excluded from the study. Results: Out of 400 individuals, 200 showed cardiac activity in the lower limb veins on Doppler vascular ultrasound, while 200 did not show cardiac activity. On echocardiography, 204 individuals were diagnosed with tricuspid regurgitation, and 196 individuals had a competent tricuspid valve. According to the independent sample t-test the mean difference in the posterior tibial vein was 25.54 (95% CI: 24.09; 26.98), while the mean difference in the iliac vein was 2.34 (95% CI: 0.64; 4.03) among normal and tricuspid regurgitation. Conclusion: A correlation was found between the cardiac activities in the lower limb veins and tricuspid regurgitation.

Assessment of right ventricular (RV) diastolic function is not routinely carried out. This is due to standard two-dimensional imaging techniques being unreliable. Four-dimensional flow (4D flow) derived right ventricular blood flow kinetic energy assessment could circumvent the issues of the current imaging modalities. It also remains unknown whether there is an association between right ventricular blood flow kinetic energy (KE) and healthy ageing. We hypothesise that healthy ageing requires maintaining normal RV intra-cavity blood flow as quantified using KE method. The main objective of this study was to investigate the effect of healthy ageing on tricuspid through-plane flow and right ventricular blood flow kinetic energy. In this study, fifty-three healthy participants received a 4D flow cardiovascular magnetic resonance (CMR) scan on 1.5 T Philips Ingenia. Cine segmentation and 4D flow analysis were performed using dedicated software. Standard statistical methods were carried out to investigate the associations. Both RV E-wave KEiEDV (r = -0.3, P = 0.04) and A-wave KEiEDV (r = 0.42, P < 0.01) showed an association with healthy ageing. Additionally, the right ventricular blood flow KEiEDV E/A ratio demonstrated the strongest association with healthy ageing (r = -0.53, P < 0.01) when compared to all RV functional and haemodynamic parameters. Furthermore, in a multivariate regression model, KEiEDV E/A ratio and 4D flow derived tricuspid valve stroke volume demonstrated independent association to healthy ageing (beta -0.02 and 0.68 respectively, P < 0.01). Ageing is independently associated with 4D flow derived tricuspid stroke volume and RV blood flow KE E/A ratio. These novel 4D flow CMR derived imaging markers have future potential for RV diastolic assessment.

Our aim is to investigate the elevation of matrix proteins in tissues obtained from distal, above the sinotubular junction (proximal), concave, and convex sites of aneurysms in the ascending aorta using a simultaneous multiplex protein detection system. Tissues were collected from 41 patients with ascending aortic aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV), whereas 10 had a tricuspid aortic valve (TAV). Concave and convex aortic site samples were collected from all patients, whereas proximal and distal convexity samples were obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous detection of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was performed at each of the four aortic sites. MMP-2 levels were higher in the concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels were higher in the convex sites than in the concave sites, as were MMP-9 levels. In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly elevated in the sinotubular proximal aorta of BAV patients. Simultaneous detection of MMPs and TIMPs revealed different levels at different aortic sites in the same patient.

Functional tricuspid regurgitation (TR) is common among patients with left heart disease and may recur during the follow-up period after selective tricuspid valve annuloplasty (TVA). This study aims to analyse the relationship between left atrial (LA) strain and the degree of preoperative functional TR and to explore the role of LA strain in predicting TR recurrence.

Cellular and molecular mechanisms of thoracic aortic aneurysm are not clear and therapeutic approaches are mostly absent. Thoracic aortic aneurysm is associated with defective differentiation of smooth muscle cells (SMC) of aortic wall. Bicuspid aortic valve (BAV) comparing to tricuspid aortic valve (TAV) significantly predisposes to a risk of thoracic aortic aneurysms. It has been suggested recently that BAV-associated aortopathies represent a separate pathology comparing to TAV-associated dilations. The only proven candidate gene that has been associated with BAV remains NOTCH1. In this study we tested the hypothesis that Notch-dependent and related TGF-β and BMP differentiation pathways are differently altered in aortic SMC of BAV- vs. TAV-associated aortic aneurysms. SMC were isolated from aortic tissues of the patients with BAV- or TAV-associated aortic aneurysms and from healthy donors used as controls. Gene expression was verified by qPCR and Western blotting. For TGF-β induced differentiation SMC were treated with the medium containing TGF-β1. To induce proosteogenic signaling we cultured SMC in the presence of specific osteogenic factors. Notch-dependent differentiation was induced via lentiviral transduction of SMC with activated Notch1 domain. MYOCD expression, a master gene of SMC differentiation, was down regulated in SMC of both BAV and TAV patients. Discriminant analysis of gene expression patterns included a set of contractile genes specific for SMC, Notch-related genes and proosteogenic genes and revealed that control cells form a separate cluster from both BAV and TAV group, while BAV- and TAV-derived SMC are partially distinct with some overlapping. In differentiation experiments TGF-β caused similar patterns of target gene expression for BAV- and TAV derived cells while the induction was higher in the diseased cells than in control ones. Osteogenic induction caused significant change in RUNX2 expression exclusively in BAV group. Notch activation induced significant ACTA2 expression also exclusively in BAV group. We show that Notch acts synergistically with proosteogenic factors to induce ACTA2 transcription and osteogenic differentiation. In conclusion we have found differences in responsiveness of SMC to Notch and to proosteogenic induction between BAV- and TAV-associated aortic aneurysms.

Since the beginning of the SARS-CoV-2 (COVID-19) pandemic, correlation of venous thromboembolism (VTE) and COVID-19 infection has been well established. Increased inflammatory response in the setting of COVID-19 infection is associated with VTE and hypercoagulability. Venous and arterial thrombotic events in COVID-19 infection have been well documented; however, few cases have been reported involving cardiac valve prostheses. In this review, we present a total of eight cases involving COVID-19-related prosthetic valve thrombosis (PVT), as identified in a systematic review. These eight cases describe valve position (mitral versus aortic) and prosthesis type (bioprosthetic versus mechanical), and all cases demonstrate incidents of PVT associated with simultaneous or recent COVID-19 infection. None of these eight cases display obvious non-adherence to anticoagulation; five of the cases occurred greater than three years after the most recent valve replacement. Our review offers insights into PVT in COVID-19 infected patients including an indication for increased monitoring in the peri-infectious period. We explore valve thrombosis as a mechanism for prosthetic valve failure. We describe potential differences in antithrombotic strategies that may offer added antithrombotic protection during COVID-19 infection. With the growing population of valve replacement patients and recurring COVID-19 infection surges, it is imperative to explore relationships between COVID-19 and PVT.

To assess heart rhythm and predictive factors associated with sinus rhythm after one year in patients with rheumatic valve disease undergoing concomitant surgical treatment of atrial fibrillation. Operative mortality, survival and occurrence of stroke after one year were also evaluated.

To explore the micromechanical, biochemical, and microstructural differences between bicuspid aortic valve aneurysm (BAV-A) and tricuspid aortic valve idiopathic degenerative aneurysm (DA), compared with normal aorta.

Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C(4) (LTC(4)) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P=0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r=-0.46, P=0.0469) and AVA indexed for body surface area (BSA) (r=-0.498; P=0.0298) only in tricuspid aortic valves. LTC(4) (1nM) significantly elevated the mRNA levels of PARP-1 by 2.38-fold in VICs. Taken together, these data suggest that valvular DNA-damage pathways may be associated with inflammation and the stenosis severity in tricuspid aortic valves.

Bicuspid aortic valve (BAV) disease is recognized to be a syndrome with a complex and multifaceted pathophysiology. Its progression is modulated by diverse evolutionary conserved pathways, such as Notch-1 pathway. Emerging evidence is also highlighting the key role of TLR4 signaling pathway in the aortic valve pathologies and their related complications, such as sporadic ascending aorta aneurysms (AAA). Consistent with these observations, we aimed to evaluate the role of TLR4 pathway in both BAV disease and its common complication, such as AAA. To this aim, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1 ± 12.8 years), with and without AAA were enrolled. Plasma assessment, tissue and gene expression evaluations were performed. Consistent with data obtained in the previous study on immune clonotypic T and B altered responses, we found reduced levels of systemic TNF-α, IL-1, IL-6, IL-17 cytokines in BAV cases, either in the presence or absence of AAA, than TAV cases (p < 0.0001 by ANOVA test). Interestingly, we also detected reduced levels of s-TLR4 in BAV cases with or without AAA in comparison to the two groups of TAV subjects (p < 0.0001 by ANOVA test). These results may suggest a deregulation in the activity or in the expression of TLR4 signaling pathway in all BAV cases. Portrait of these data is, indeed, the significantly decreased gene expression of inflammatory cytokines and TLR4, in both normal and aneurysmatic tissue samples, from BAV with AAA than TAV with AAA. In conclusion, our study demonstrates that subjects with BAV display a significant deregulation of TLR4 signaling pathway paralleled by a deregulation of Notch-1 pathway, as previously showed. This data suggests that the crosstalk between the Notch-1 and TLR4 signaling pathways may play a crucial role in both physiological embryological development, and homeostasis and functionality of aortic valve in adult life.

Triple valve surgery is usually complex and carries a reported operative mortality of 13% and 10-yr survival of 61%. We examined surgical results based on our hospital's experience. A total of 160 consecutive patients underwent triple valve surgery from 1990 to 2006. The most common aortic and mitral valve disease was rheumatic disease (82%). The most common tricuspid valve disease was functional regurgitation (80%). Seventy-four percent of the patients were in New York Heart Association (NYHA) class III and IV. Univariate and multivariable analyses were performed to identify predictors of early and late survival. Operative mortality was 6.9% (n=11). Univariate factors associated with mortality included old age, preoperative renal failure, postoperative renal failure, pulmonary complications, and stroke. Of them, postoperative renal failure and stroke were associated with mortality on multivariable analysis. Otherwise, neither tricuspid valve replacement nor reoperation were statistically associated with late mortality. Survival at 5 and 10 yr was 87% and 84%, respectively. Ninety-two percent of the patients were in NYHA class I and II at their most recent follow-up. Ten-year freedom from prosthetic valve endocarditis was 97%; from anticoagulation-related hemorrhage, 82%; from thromboembolism, 89%; and from reoperation, 84%. Postoperative renal failure and stroke were significantly related with operative mortality. Triple valve surgery, regardless of reoperation and tricuspid valve replacement, results in acceptable long-term survival.

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as compared to persons with a tricuspid aortic valve. Due to the high prevalence of a BAV in the general population and the associated life-long increased risk for adverse vascular events, BAV disease places a considerable burden on the public health. The aim of the present review is to discuss the role of transforming growth factor beta (TGF-β) signaling in the development of the vascular wall and on how this complex signaling pathway may be involved in thoracic aortic aneurysm formation in tricuspid and BAV patients.

Catheter-tissue contact force is an important factor influencing lesion size and efficacy and thereby potential for arrhythmia recurrence following accessory pathway (AP) radiofrequency ablation. We aim to evaluate adequacy and perception of catheter contact on the tricuspid and mitral annuli.

Coarctation of the aorta is a form of left ventricular outflow tract obstruction in paediatric patients that can be presented with either bicuspid (BAV) or normal tricuspid (TAV) aortic valve. The congenital BAV is associated with hemodynamic changes and can therefore trigger different molecular remodelling in the coarctation area. This study investigated the proteomic and phosphoproteomic changes associated with BAV for the first time in neonatal coarctation patients. Aortic tissue was collected just proximal to the coarctation site from 23 neonates (BAV; n = 10, TAV; n = 13) that were matched for age (age range 4-22 days). Tissue from half of the patients was frozen and used for proteomic and phosphoproteomic analysis whilst the remaining tissue was formalin fixed and used for analysis of elastin content using Elastic Van-Gieson (EVG) staining. A total of 1796 protein and 75 phosphoprotein accession numbers were detected, of which 34 proteins and one phosphoprotein (SSH3) were differentially expressed in BAV patients compared to TAV patients. Ingenuity Pathway Analysis identified the formation of elastin fibres as a significantly enriched function (p = 1.12 × 10-4) due to the upregulation of EMILIN-1 and the downregulation of TNXB. Analysis of paraffin sections stained with EVG demonstrated increased elastin content in BAV patients. The proteomic/phosphoproteomic analysis also suggested changes in inositol signalling pathways and reduced expression of the antioxidant SOD3. This work demonstrates for the first time that coarcted aortic tissue in neonatal BAV patients has an altered proteome/phosphoproteome consistent with observed structural vascular changes when compared to TAV patients.

Calcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with patients having normal valves, using a knowledge-slanted random forest (RF).

Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysm. In the present study, collagen homeostasis in nondilated and dilated aorta segments from patients with BAV was studied, with normal and dilated aortas from tricuspid aortic valve (TAV) patients as reference.

Background To characterize the development of sick sinus syndrome ( SSS ) after the additive maze procedure ( MP ) during mitral valve surgery. Methods and Results Follow-up data (median, 3.6 years) of 750 patients with a prevalence of rheumatic cause of 57.6% were analyzed. SSS occurred in 35 patients with a time-dependent increase: the incidence rates at 1, 2, and 4 years after surgery were 2.9%, 3.7%, and 4.3%, respectively. The additive MP showed higher risks of SSS development (hazard ratio, 7.44; 95% confidence interval, 3.45-16.05; P<0.001) and pacemaker implantation (hazard ratio, 3.61; 95% confidence interval, 1.95-6.67; P<0.001). Patients who developed SSS showed higher 4-year rates of clinical events (death, stroke, and hospital admission) (67.5±8.5% versus 33.0±1.9%; P<0.001). After adjustment for age and preoperative peak systolic pulmonary artery pressure, the lesion extent (biatrial versus left atrial MP ), not the underlying cause (rheumatic versus nonrheumatic), was independently associated with SSS development (hazard ratio, 3.58; 95% confidence interval, 1.08-11.86; P=0.037). The adverse effect of the biatrial MP was confirmed in patients with trivial or mild preoperative tricuspid regurgitation showing higher SSS incidence (4.6±1.4% versus 1.0±0.7%; P=0.023), not in those with moderate-to-severe tricuspid regurgitation (6.8±1.7% versus 3.8±3.8%; P=0.337). Recurrence of atrial fibrillation was not associated with the lesion extent of the MP . Conclusions After the additive MP , the ongoing risk of SSS development should be acknowledged irrespective of the underlying cause. Considering additive risk of biatrial MP with similar atrial fibrillation recurrence rate, minimizing lesion extent is warranted.