UNASSIGNED: The ideal position of suture annuloplasty relative to the aortic annulus (internal or external) remains unclear. This study aimed to investigate the effectiveness of internal and external suture annuloplasty for isolated type 1 bicuspid aortic valve (BAV) repair. Electrocardiogram (ECG)-gated computed tomography (CT) was used to compare the two techniques and analyze their impact on the aortic annulus.
UNASSIGNED: We retrospectively analyzed 20 patients who underwent isolated type 1 BAV repair with either internal or external suture annuloplasty. Each group included 10 patients with comparable clinical features. Preoperative and postoperative ECG-gated CT scans were performed to assess the anatomical relationship between the ventricular-aortic junction (VAJ) and virtual basal ring (VBR), and to measure the height of annuloplasty from the VBR at predefined landmarks in both groups. Perioperative annular geometries, including annular area and perimeter, were measured to quantify the impact of annuloplasty on annular expansibility. The discrepancy between the postoperative annular dimension and size of the Hegar dilator were compared between groups to evaluate the effectiveness of annuloplasty.
UNASSIGNED: In both groups, VAJ was higher than VBR at the right coronary (RC) ostium (7.7 ± 3.3 mm) and the raphe (7.9 ± 1.5 mm). The height from the VBR to the external suture annuloplasty shared a similar pattern at the RC ostium and raphe (5.3 ± 1.1 mm and 4.8 ± 1.0 mm, respectively). In contrast, the height differences were minimal for these landmarks in the internal group. Postoperative annular area expansibility decreased in the internal group compared to preoperative levels (4.9 ± 2.3% vs. 8.9 ± 5.5%, p = 0.038), while no significant change was found in the external group (7.6 ± 4.1% vs. 6.5 ± 2.8%, p = 0.473). The internal group showed less area discrepancy between the VBR and the Hegar dilator both at systole (10.1 ± 3.7% vs. 30.1 ± 16.6%, p = 0.004) and diastole (5.7 ± 4.9% vs. 20.9 ± 14.5%, p = 0.009) compared to the external group.
UNASSIGNED: Internal suture annuloplasty results in better positioning relative to the VBR than external suture annuloplasty due to the absence of VAJ interference. While this results in more precise annular reduction and less expansibility in the short term, a long-term follow-up evaluation is necessary to assess its effectiveness.

OBJECTIVE: Bicuspid aortic valve (BAV) is prone to promote left ventricular remodeling (LVR), which is associated with adverse clinical outcomes. Although the association between angiogenic activity and LVR has been established, pro-angiogenic cytokine features and potential biomarker candidates for LVR in patients with BAV remain to be clarified.
METHODS: From November 2018 to May 2019, patients with BAV diagnosed by transthoracic echocardiography at our institution were included. LVR was diagnosed on the basis of echocardiographic calculations of relative wall thickness (RWT) and left ventricular mass index (LVMI). A multiplex ELISA array was used to measure the plasma levels of 60 angiogenesis-related cytokines.
RESULTS: Among 103 patients with BAV, 71 were categorized into the LVR group and 32 into the normal left ventricular (LV) geometry group. BAV patients with LVR demonstrated increased LVMI, elevated prevalence of moderate to severe aortic stenosis and aortic regurgitation, and decreased LV ejection fraction (LVEF). Plasma levels of angiopoietin-1 were elevated in BAV patients with or without LVR compared with healthy controls (P = 0.001, P < 0.001, respectively), and were negatively correlated with RWT (r = -0.222, P = 0.027). Plasma levels of angiopoietin-2 were elevated in the LVR group (P = 0.001) compared with the normal LV geometry group, and were negatively correlated with LVEF (r = -0.330, P = 0.002).
CONCLUSIONS: Decreased angiogenesis plays a crucial role in the occurrence and progression of LVR in patients with BAV. Disturbance in the pro- and anti-angiogenesis equilibrium in BAV patients with LVR may reflect the aggravation of endothelial injury and dysfunction.

OBJECTIVE: The aims of the present study were to compare the long-term outcomes for ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve ( TAV).
METHODS: This retrospective study included 310 patients who had undergone isolated aortic valve replacement with an ascending aorta diameter ≤ 45 mm between January 2010 and September 2021. The patients were divided into BAV group (n=90) and TAV group (n=220). The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed.
RESULTS: Overall survival was 89 ± 4% in the BAV group vs. 75 ± 6% in the TAV group at 10 years postoperatively (P=0.007), yet this difference disappeared after adjusting exclusively for age (P=0.343). The mean annual growth rate of the ascending aorta was similar between the two groups during follow-up (0.5 ± 0.6 mm/year vs. 0.4 ± 0.5 mm/year; P=0.498). Ten-year freedom from adverse aortic events was 98.1% in the BAV group vs. 95.0% in the TAV group (P=0.636). Multivariable analysis revealed preoperative ascending aorta diameter to be a significant predictor of adverse aortic events (hazard ratio: 1.76; 95% confidence interval: 1.33 to 2.38; P<0.001).
CONCLUSIONS: Our study revealed that the long-term survival and the risks of adverse aortic events between BAV and TAV patients were similar after isolated aortic valve replacement. BAV was not a risk factor of adverse aortic events.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR).
OBJECTIVE: The aim of this study was to identify the incidence, predictors, and clinical outcomes of PVR after TAVR in Sievers type 1 BAV stenosis.
METHODS: Consecutive patients with Sievers type 1 BAV stenosis undergoing TAVR with current-generation transcatheter heart valves (THVs) in 24 international centers were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAEs), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up.
RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%)-mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were a larger virtual raphe ring perimeter (adjusted OR: 1.07; 95% CI: 1.02-1.13), severe annular or left ventricular outflow tract calcification (adjusted OR: 5.21; 95% CI: 1.45-18.77), a self-expanding valve (adjusted OR: 9.01; 95% CI: 2.09-38.86), and intentional supra-annular THV positioning (adjusted OR: 3.31; 95% CI: 1.04-10.54). At a median follow-up of 1.3 years (Q1-Q3: 0.5-2.4 years), moderate or severe PVR was associated with an increased risk of MAEs (adjusted HR: 2.52; 95% CI: 1.24-5.09).
CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAEs during follow-up.

UNASSIGNED: In mixed aortic valve disease (MAVD), the results of transcatheter aortic valve replacement (TAVR) are conflicting. There is limited data on the outcomes of TAVR in patients with bicuspid aortic valve (BAV) and MAVD. The objective of this study is to compare outcomes after TAVR in BAV patients with MAVD and predominant aortic stenosis (PAS).
UNASSIGNED: Patients with BAV who underwent TAVR between January 2016 and April 2023 were included. The primary outcome was device success. The secondary endpoints were periprocedural mortality and other complications as defined by the Valve Academic Research Consortium-3 (VARC-3). Propensity score matching was used to minimize potential confounding.
UNASSIGNED: A total of 262 patients were included in this study, 83 of whom had MAVD. The median age was 72 years, and 55.7% were male. The baseline comorbidity risk files were comparable between the two groups. Patients with MAVD had more mitral regurgitation, tricuspid regurgitation and pulmonary hypertension, larger annular and left ventricular outflow tract dimensions, and more severe calcification than PAS. In the unmatched population, MAVD patients had similar device success rate (69.9% vs 79.9%, P=0.075) and 30-day mortality (3.6% vs 3.4%, P=1) compared to PAS. Propensity score matching resulted in 66 patient pairs. Device success rate were still comparable in the matched population. Other clinical outcomes, including stroke, bleeding (type 2-4), major vascular complications, acute kidney injury (stage 2-4) and permanent pacemaker implantation, were comparable between the two groups. Multivariable logistic regression analysis did not show MAVD to be an independent negative predictor of device success. At one year, survival was similar between patients with MAVD and those with PAS.
UNASSIGNED: For the bicuspid valve, patients with MAVD had a more challenging anatomy. MAVD patients associated with comparable 30-day clinical outcomes after TAVR compared to PAS patients in patients with BAV.

UNASSIGNED: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiovascular defect and known to cause thoracic aortic aneurysms (TAAs). To improve our understanding of BAV pathogenesis, we characterized the cellular composition of BAV tissues and identified molecular changes in each cell population.
UNASSIGNED: Tissue samples from two patients with BAV and two heart transplant donors were analyzed using single-cell RNA sequencing, assay for transposase-accessible chromatin using sequencing, and weighted gene coexpression network analysis for differential gene analysis. TAA-related changes were evaluated by comparing the proportion of each cell type and gene expression profiles between TAA and control tissues. Further, by combining our single-cell RNA sequencing data with publicly available data from genome-wide association studies, we determined critical genes for BAV.
UNASSIGNED: We found 20 cell subpopulations in TAA tissues, including multiple subtypes of smooth muscle cells, fibroblasts, macrophages, and T lymphocytes. This result suggested that these cells play multiple functional roles in BAV development. Several differentially expressed genes, including CD9, FHL1y, HSP90AA1, GAS6, PALLD, and ACTA2, were identified.
UNASSIGNED: We believe that this comprehensive assessment of the cellular composition of TAA tissues and the insights into altered gene expression patterns can facilitate identification of novel diagnostic biomarkers and therapeutic targets for BAV-associated TAA.

Both ageing and hypertension are clinical factors that may lead to a higher propensity for dissection or rupture of ascending thoracic aortic aneurysms (ATAAs). This study sought to investigate effect of valve morphology on regional delamination strength of ATAAs in the elderly hypertensive patients. Whole fresh ATAA samples were harvested from 23 hypertensive patients (age, 71 ± 8 years) who underwent elective aortic surgery. Peeling tests were performed to measure region-specific delamination strengths of the ATAAs, which were compared between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The regional delamination strengths of the ATAAs were further correlated with patient ages and aortic diameters for BAV and TAV groups. In the anterior and right lateral regions, the longitudinal delamination strengths of the ATAAs were statistically significantly higher for BAV patients than TAV patients (33 ± 7 vs. 23 ± 8 mN/mm, p = 0.01; 30 ± 7 vs. 19 ± 9 mN/mm, p = 0.02). For both BAV and TAV patients, the left lateral region exhibited significantly higher delamination strengths in both directions than the right lateral region. Histology revealed that disruption of elastic fibers in the right lateral region of the ATAAs was more severe for the TAV patients than the BAV patients. A strong inverse correlation between longitudinal delamination strength and age was identified in the right lateral region of the ATAAs of the TAV patients. Results suggest that TAV-ATAAs are more vulnerable to aortic dissection than BAV-ATAAs for the elderly hypertensive patients. Regardless of valve morphotypes, the right lateral region may be a special quadrant which is more likely to initiate dissection when compared with other regions.

OBJECTIVE: The conventional valve stents that are cylindrical in shape will become elliptical when implanted in bicuspid aortic valve, thereby reducing the durability of the artificial valve. In this study, a new design of valve stent is presented where valve stents have elliptical cross-section at the annulus and it is expected to have better expandability and circle shape during the interaction between the stent and bicuspid aortic valve, thereby extending the durability of artificial valve.
METHODS: Finite element method (FEM) is used to study the mechanical behavior of the novel valve stent in the bicuspid aortic valve. The effects of three matching relationship between the ellipticity of the stents and the ellipticity of the annulus (i.e., the ellipticity of the stent is greater than, equal to and less than the annulus ellipticity, respectively) on the mechanical behavior of stent expansion are studied. In addition, the expansion mechanical behavior of the novel valve stent at different implantation depths is also compared.
RESULTS: Results indicate that novel valve stent implantation with elliptical features is superior to conventional circular valve stent. When the novel valve stent ellipticity is less than the annulus ellipticity, the ellipticity of the novel valve stent after implantation is smaller than that of the conventional circular valve stent. This indicated that the novel valve stent has better expandability and post-expansion shape, making artificial valve to have better durability. The risk of paravalvular leak after implantation is lowest when the novel valve stent ellipticity is less than annulus ellipticity. When the novel valve stent ellipticity coincides with annulus ellipticity, the aortic wall is subjected to greatest stress. With the increase of implantation depth, the stress on the novel valve stent decrease.
CONCLUSIONS: This study might provide insights for improving stent design for bicuspid aortic valve.

BACKGROUND: Left atrial reservoir strain (LARS) is a novel imaging biomarker of left ventricular diastolic dysfunction. This study aimed to examine the prognostic implications of LARS in patients with bicuspid aortic valve and significant (moderate-severe to severe) aortic regurgitation.
RESULTS: A total of 220 patients with bicuspid aortic valve and significant aortic regurgitation were prospectively enrolled in our study. LARS and left ventricular global longitudinal strain were derived from speckle-tracking echocardiography. The end point was a composite of all-cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The threshold value of LARS <24% was used to identify impaired left atrial mechanics based on prior results. During a median follow-up of 364 (interquartile range, 294-752) days, 46 patients (20.9%) reached the composite end points. On multivariable Cox analysis, impaired LARS (adjusted hazard ratio, 2.08 [95% CI, 1.05-4.11]; P=0.036) was a statistically significant predictor of composite end points after adjustment for other statistically significant predictors. Finally, adding impaired LARS to other statistically significant predictors (New York Heart Association functional class and left ventricular global longitudinal strain) significantly improved the global χ2 (from 32.19 to 36.56; P=0.037) and reclassification (continuous net reclassification index=0.55; P<0.001) of the prediction model.
CONCLUSIONS: In patients with bicuspid aortic valve and significant aortic regurgitation, the impairment of LARS is a strong independent prognostic predictor and confers incremental prognostic utility over clinical and other echocardiographic parameters. These findings suggest that LARS could be considered in risk stratification for such populations.

BACKGROUND: We aim to compare the short and long-term outcomes for aortic stenosis (AS) patients undergone TAVR with and without ascending aorta dilation (AAD).
METHODS: Consecutive patients diagnosed with native severe AS who underwent TAVR from September 2012 to September 2021 were enrolled. They were stratified into the moderate/severe dilation group (greatest ascending aorta width ≥ 45 mm) and the non/mild dilation group. Survival outcomes were illustrated using Kaplan-Meier curves and evaluated with the log-rank test. Data from patients with CT follow-up of >6 months was used to investigate the progression rate of AAD.
RESULTS: The study cohort comprised 556 patients, with a mean age of 75.5 ± 7.3 years. Among them, 107 patients (19.2%) had a moderate/severe AAD (≥45 mm), with an average diameter of 48.6 mm (±2.8). During hospitalization, both groups witnessed two cases of ascending aortic dissection (1.9% vs 0.4%, P = 0.380). The median follow-up duration was 3.9 years (95% CI: 3.8-4.0 years). No deaths were caused by aortic events and no patients experienced a new aortic dissection. The AAD cohort\'s 4-year all-cause and cardiovascular mortality rates were not significantly different to the non/mild dilation group\'s (log-rank test, P = 0.109 and P = 0.698, respectively). Follow-up CT data revealed that the rate of aortic dilation progression in the moderate/severe dilation group was not significantly different from that in the non/mild group (0.0 mm/year, 25-75%th: -0.3-0.2 vs 0.1 mm/year, 25-75%th: -0.3-0.4, P = 0.122).
CONCLUSIONS: This study found no significant difference regarding short-term and long-term outcomes in AS patients with/without moderate/severe AAD undergoing TAVR.