Tricuspid Aortic Valve Patients Research Articles

Association between silent cerebral embolism and cognitive alterations following transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valve patients

Abstract Background Silent cerebral ischemic lesions (SCILs) is a common magnetic resonance imaging (MRI) finding in severe aortic stenosis patients post - transcatheter aortic valve replacement (TAVR). We evaluated the association between SCILs and cognitive alterations in patients with bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) post-TAVR. Methods This study enrolled 100 consecutive TAVR (45 with BAV and 55 TAV). DW-MRI and neurocognitive evaluation (MoCA score) were performed at baseline, discharge, and 1- and 12-month post-discharge. Results Ninety-two out of the 100 patients (92%) exhibited cognitive dysfunction at baseline. Post-TAVR, overall cognitive function significantly improved, the average MOCA score increased from 18.69±6.74 to 22.18±6.30. During the 1-year follow-up, 54 patients demonstrated improved cognitive function, and the number of patients with moderate-to-severe cognitive dysfunction (MoCA score < 18) significantly decreased from 32 to 16. Prevalence of SCILs was 14% and 72% at baseline and discharge, respectively. New SCILs were observed in 60 patients at discharge, distributed across all vascular territories, averaging 4 lesions with a total volume of 215.4±195.4mm3. Although no significant correlation existed between total volume of new SCILs and cognitive changes post-TAVR (R=-0.133, p=0.206), patients with SCILs still displayed significant cognitive improvement (MoCA score from 18.4±6.6 to 22.0±7.1), whereas patients who developed large SCILs (lesion diameter >9) showed less improvement compared to those with small or median SCILs (number of patients who had cognitive improvement: 32 vs. 52, p<0.05). Cognitive function improvement post-TAVR did not significantly differ between BAV and TAV patients, MoCA scores were comparable (BAV group, n=45, from 18.63±6.68 to 21.88±6.80 vs. TAV group, n=55, from 18.73±6.81 to 22.42±5.80; p>0.05). DW-MRI revealed more new SCILs in BAV patients post-TAVR compare to TAV patients (235 lesions vs. 150 lesions, respectively). In BAV patients, SCILs primarily manifested in small and medium sizes (224 lesions), despite more severe calcification (valvular calcium volume 956.5±644.0 mm vs. 634.4±508.0 mm3; p=0.028). The number of large lesions was similar in the two groups (11 in BAV group and 10 in TAV group). Conclusion TAVR demonstrates positive effects on improving cognitive function in aortic stenosis patients, despite common occurrence of SCILs in both BAV and TAV patients. Cognitive function post-TAVR was comparable between BAV and TAV patients. The cognitive improvement from TAVR may be less impacted by small- and medium-sized SCILs, while severe SCILs might impede or diminish the cognitive benefits of TAVR.table

Indexed aortic valve area using multimodality imaging for assessing the severity of bicuspid aortic stenosis

BackgroundThe impact of various imaging modalities on discordance/concordance between indexed aortic valve area (iAVA) and catheterization-derived mean transaortic pressure gradient (mPGcath) is unclear in patients with bicuspid aortic valve (BAV). This study aimed to compare iAVA measurements obtained using four different methodologies in BAV and tricuspid aortic valve (TAV) patients, using mPGcath as a reference standard. MethodsWe retrospectively reviewed patients who underwent comprehensive assessment of AS, including two-dimensional (2D) transthoracic echocardiography (TTE), three-dimensional (3D) transesophageal echocardiography (TEE), multidetector computed tomography (MDCT), and catheterization, at our institution between 2019 and 2022. iAVA was measured using the continuity eq. (CE) with left ventricular outflow tract area obtained by 2D TTE, 3D TEE, and MDCT, as well as planimetric 3D TEE. Results and ConclusionsAmong 564 patients (64 with BAV and 500 with TAV), 64 propensity-matched pairs of patients with BAV and TAV were analyzed. iAVACE(2DTTE) led to overestimation of AS severity (BAV, 23.4%; TAV, 28.1%) and iAVACE(MDCT) led to underestimation of AS severity (BAV, 29.3%; TAV, 16.7%), whereas iAVACE(3DTEE) and iAVAPlani(3DTEE) resulted in a reduction in the discordance of AS grading. A moderate correlation was observed between mPGcath and iAVACE(3DTEE) (BAV, r = −0.63; TAV, r = −0.68), with iAVACE(3DTEE) corresponding to the current guidelines' cutoff value (BAV, 0.58 cm2/m2; TAV, 0.60 cm2/m2). Discordance/concordance between iAVA and mPGcath in evaluating AS severity varies depending on the methodology and imaging modality used. The use of iAVACE(3DTEE) is valuable for reconciling the discordant AS grading in BAV patients as well as TAV.

Metabolic plasma signatures in thoracic aortic aneurysm associated to tricuspid and bicuspid aortic valves

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III with co-funding from the ERDF and Comunidad de Madrid Background/Introduction Thoracic aortic aneurysm (TAA) develops asymptomatic with life-threatening consequences and its diagnosis is usually fortuitous. TAA is mostly idiopathic, although its prevalence is significantly higher in subjects with bicuspid aortic valve (BAV) for unknown reasons. We hypothesize that it is essential to investigate idiopathic TAA by differentiating between BAV and tricuspid aortic valve (TAV) patients for personalized diagnosis and treatment. Purpose We aimed to identify plasma metabolic profiles of aortic dilatation in idiopathic TAA, differentiating between subjects with BAV or TAV. Methods Plasma samples from 41 idiopathic TAA patients and 57 subjects without aortic dilatation (control, C) were collected and classified according to aortic valve type (BAV or TAV). Full metabolomics coverage was carried out by 1H RMN and LC-MS/MS untargeted analysis, including reverse phase and hydrophilic interaction chromatography and positive and negative electrospray ionization modes. Significant variation in metabolite levels were considered if FDR-adjusted p-value <0.05. Results Our analyses highlighted a metabolic signature specific for BAV and TAV subjects. BAV patients presented a marked glycerophospholipid metabolism alteration involving different lysophospholipids (LPAs, LPCs and LPEs) and phospholipids (PCs, PEs, PAs and PIs). Particularly, LPCs and LPEs were increased in BAV-TAA vs BAV-C, being an indicator of stimulation of glucose utilization through glycolysis and suppression of fatty acid biosynthesis. In contrast, carnitine-related metabolism was the most altered pathway observed in TAV subjects. In particular, we detected an increment in plasma acylcarnitines in TAV-TAA compared to TAV-C suggesting an altered β-oxidation of fatty acids and mitochondrial overload. Conclusions Idiopathic TAA development is differentially reflected in plasma from BAV and TAV patients, supporting an individualized diagnosis valve-dependent and suggesting also differential therapeutic targets.

Spatially resolved metabolomics revealed specific nucleotide alterations within the media and adventitia layers in idiopathic thoracic aortic aneurysms associated with tricuspid and bicuspid valves

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III co-supported by FEDER grants and co-funded by the European Union Background Thoracic aortic aneurysms (TAAs) curse silently and asymptomatic. The vast majority are idiopathic, representing 80-95% of the cases. Nevertheless, there is an association between TAA and the presence of bicuspid aortic valve (BAV) constituting BAV an independent risk factor of TAA. The presence of BAV accelerates the growth of the aneurysm affecting younger patients than those with tricuspid aortic valve (TAV). Evidence points to a profound remodeling of the media and adventitia layers, but the underlying mechanisms are unknown, especially the metabolic changes taking place and their in situ localization. Purpose Our aim was to identify, in a spatially resolved manner, the in situ metabolic alterations occurring in TAA human aortas while differentiating between BAV and TAV patients. In a further step, we sought to identify the changes happening particularly within the media and adventitia layers. Methods Mass spectrometry imaging (MSI) was applied to identify metabolic differences between human aortas with (TAA) and without (C) dilatation classified according to their aortic valve and obtained from cardiac surgeries. Clinical groups consisted on TAV-C (n=11), BAV-C (n=12), TAV-TAA (n=12) and BAV-TAA (n=12). Subsequent virtual microdissection histologically guided was applied to identify the specific metabolic changes located within media and/or adventitia. Changes were considered significant if FDR>2 and p-value <0.05. Results Purine metabolism resulted altered in BAV-TAA patients while no differences were found in TAV-TAA ones. Particularly, we detected a significant increase of aortic ATP (FC= 2.92; p-value= 0.030), ADP (FC= 2.04; p-value= 0.020), AMP (FC= 2.42; p-value= 0.011) and GDP (FC= 2.29; p-value= 0.046) in BAV-TAA vs. BAV-C subjects. In contrast, we found an in situ increment in pyrimidine metabolism resulting UDP and UMP increased in both, TAV and BAV associated TAAs. When comparing the arterial layers, media layer was found to be the major driver of BAV-TAA with no nucleotides changes in adventitia. However, TAV-TAA media and adventitia layer behave similarly with the exception of a massive increase of ATP (FC=50.23, p=0.046) in adventitia with no alteration in media of TAV-TAA vs. TAV-C patients. Conclusions Idiopathic TAAs course differently in subjects with bicuspid and tricuspid valves both in terms of mechanisms of action and arterial remodeling within the aortic layers. These findings suggest that TAA patients with bicuspid or tricuspid aortic valve should be treated as independent groups for optimal disease management.

Off-Label Use of Balloon-Expandable Transcatheter Valves to Treat Pure Aortic Regurgitation

Transcatheter aortic valve implantation (TAVI) in native pure aortic regurgitation (AR) with off-label use of balloon expandable valves (BEV) has been reported. However, there are scant data regarding optimal oversizing and its safety and our study assessed BEV oversizing and outcomes of TAVI. Thirteen consecutive tricuspid aortic valve patients undergoing transfemoral TAVIs for pure AR with Sapien BEV at our centre between 2019 and 2023 (69.2% males, mean age 80.8 years, STS 4.0%) were divided into small annulus group (≤618mm2, SA) where ≥20% oversizing is achievable based on published data on BEV overexpansion, and larger annulus group (LA, >618mm2). Overexpansion and actual oversizing were measured on post-procedural CT scan. Technical success was 92.3% with one valve embolization in LA group. The post-procedural CT showed a mean 28.3% oversizing, significantly higher in SA (31.2%) then in LA group (19.4%), p= 0.0092. Oversizing ≥20% was achieved in 100% SA vs 33.3% LA patients (p=0.046). In conclusion, TAVI in pure AR with oversized Sapien BEV showed good procedural and short-term outcomes when ≥20% oversizing was predictably achievable.

Midterm durability of valve-sparing root replacement in bicuspid and tricuspid aortic valves

Background Among patients with bicuspid aortic valves (BAV) who are potential candidates for valve-sparing root replacement (VSRR), the long-term durability of this technique is not well understood. This study aimed to compare the clinical and echocardiographic outcomes of VSRR in those with BAV and tricuspid aortic valve (TAV) morphology. Methods This was a retrospective analysis of patients who underwent VSRR between 2007 and 2021 at a single center. Kaplan-Meier and log-rank analysis were used to estimate and compare freedom from mortality, progression to >2+ aortic insufficiency (AI), and reoperation between groups (BAV vs TAV). Preoperative and postoperative echocardiographic data were collected and assessed for temporal changes in mixed-effect models. Results A total of 185 patients (BAV, n = 52, 28.1%; TAV, n = 133, 71.9%) underwent VSRR. At baseline, BAV patients were younger (42.4 ± 11.6 vs 52.3 ± 12.6 years; P < 0.01) and had more severe AI (47.9% vs 27.0%; P = 0.02). Average cardiopulmonary bypass and cross-clamp times were similar. There were no differences in rates of postoperative complications, intensive care unit or hospital days, or 30-day readmission. TAV patients’ 1-, 5-, and 8-year survival rates were 99.2% [95% CI 97.8–100], 96.7% [93.5–99.9%], and 92.2% [85.6–99.3%], respectively. Overall, there were no differences between groups regarding freedom from mortality (P = 0.18), reoperation (P = 0.51), or recurrent >2+ AI (P = 0.97). Conclusions VSRR can be safely performed on patients with BAV and TAV morphology, yielding similar midterm freedom from mortality, recurrent >2+ AI, and reoperation. This technique should be considered in carefully selected patients with aortic root pathology and BAV anatomy when performed at experienced centers.

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients.

Thoracic aortic aneurysm (TAA) is mainly sporadic and with higher incidence in the presence of a bicuspid aortic valve (BAV) for unknown reasons. The lack of drug therapy to delay TAA progression lies in the limited knowledge of pathophysiology. We aimed to identify the molecular hallmarks that differentiate the aortic dilatation associated with BAV and tricuspid aortic valve (TAV). Aortic vascular smooth muscle cells (VSMCs) isolated from sporadic TAA patients with BAV or TAV were analyzed by mass spectrometry. DNA oxidative damage assay and cell cycle profiling were performed in three independent cohorts supporting proteomics data. The alteration of secreted proteins was confirmed in plasma. Stress phenotype, oxidative stress, and enhanced DNA damage response (increased S-phase arrest and apoptosis) were found in BAV-TAA patients. The increased levels of plasma C1QTNF5, LAMA2, THSB3, and FAP confirm the enhanced stress in BAV-TAA. Plasma FAP and BGN point to an increased inflammatory condition in TAV. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA. The molecular pathways identified support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients, showing specific markers in plasma which may serve to monitor therapy efficacy.

Left ventricular reverse remodeling after aortic valve replacement or repair in bicuspid aortic valve with moderate or greater aortic regurgitation

ObjectiveBicuspid aortic valve (AV) patients with aortic regurgitation (AR) differ from tricuspid AV patients given younger age, greater left ventricle (LV) compliance, and more prevalent aortic stenosis (AS). Bicuspid AV-specific data to guide timing of AV replacement or repair are lacking. MethodsAdults with bicuspid AV and moderate or greater AR who underwent aortic valve replacement or repair at our center were studied. The presurgical echocardiogram, and echocardiograms within 3 years postoperatively were evaluated for LV geometry/function, and AV function. Semiquantitative AS/AR assessment was performed in all patients with adequate imaging. ResultsOne hundred thirty-five patients (85% men, aged 44.5 ± 15.9 years) were studied (63% pure AR, 37% mixed AS/AR). Following aortic valve replacement or repair, change in LV end-diastolic dimension and change in LV end-diastolic volume were associated with preoperative LV end-diastolic dimension (β = 0.62 Δcm/cm; 95% CI, 0.43-0.73 Δcm/cm; P < .001), and LV end-diastolic volume (β = 0.6 ΔmL/mL; 95% CI, 0.4-0.7 ΔmL/mL; P < .001), respectively, each independent of AR/AS severity (P = not significant). Baseline LV size predicted postoperative normalization (LV end-diastolic dimension: odds ratio, 3.75/cm; 95% CI, 1.61-8.75/cm, LV end-diastolic volume: odds ratio, 1.01/mL; 95% CI, 1.004-1.019/mL, both P values < .01) whereas AR/AS severity did not (P = not significant). Indexed LV end diastolic volume outperformed LV end-diastolic dimension in predicting postoperative LV normalization (area under the curve = 0.74 vs 0.61) with optimal diagnostic cutoffs of 99 mL/m2 and 6.1 cm, respectively. Postoperative indexed LV end diastolic volume dilatation was associated with increased risk of death, transplant/ventricular assist device, ventricular arrhythmia, and reoperation (hazard ratio, 6.1; 95% CI, 1.7-21.5; P < .01). ConclusionsRemodeling extent following surgery in patients with bicuspid AV and AR relates to preoperative LV size independent of valve disease phenotype or severity. Many patients with LV end-diastolic dimension below current surgical thresholds did not normalize LV size. LV volumetric assessment offered superior diagnostic performance for predicting residual LV dilatation, and postoperative indexed LV end diastolic volume dilatation was associated with adverse prognosis.

Region-specific delamination strength of ascending thoracic aortic aneurysm of elderly hypertensive patients with bicuspid and tricuspid aortic valves

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.

Treatment strategies and outcomes following acute type A aortic dissection repair in patients with bicuspid and tricuspid aortic valves: A meta-analysis

BackgroundThere is no consensus regarding the strategies for repairing acute type A aortic dissection (ATAAD) in patients with bicuspid aortic valve (BAV). This meta-analysis aimed to compare the treatment strategies and outcomes of ATAAD repair between patients with BAV and those with tricuspid aortic valve (TAV). MethodsA systematic review of databases were performed from inception through March 2023. The primary outcome of interest was all-cause mortality, with a minimum follow-up of 1 year. The secondary outcomes of interest included ratios of performed procedures and rate of distal aortic reoperation. Data were extracted, and pooled analysis was performed using a random-effects model. ResultsEight observational studies including a total of 3701 patients (BAV, n = 349; TAV, n = 3352) were selected for a meta-analysis. Concerning proximal aortic procedures, BAV patients exhibited a higher incidence of necessary root replacement (odds ratio [OR], 6.53; 95% confidence interval [CI], 3.84 to 11.09; P < .01). Regarding distal aortic procedures, extended arch replacement was performed less frequently in BAV patients (OR, 0.69; 95% CI, 0.49 to 0.99; P = .04), whereas hemiarch procedure rates were comparable in the 2 groups. All-cause mortality was lower in the BAV group (hazard ratio, 0.68; 95% CI, 0.50 to 0.92; P = .01). Distal aortic reoperation rates were comparable in the 2 groups. ConclusionsThis study highlights distinct procedural patterns in ATAAD patients with BAV and TAV. Despite differing baseline characteristics, BAV patients exhibited superior survival compared to TAV patients, with comparable distal aortic reoperation rates. These findings may be useful for decision making regarding limited versus extended aortic arch repair.

Left atrial dysfunction in bicuspid aortic valve patients with severe aortic stenosis is associated with post-operative atrial fibrillation following aortic valve replacement.

To investigate (i) the association between pre-operative left atrial (LA) reservoir strain and post-operative atrial fibrillation (AF) and (ii) the incidence of post-operative ischaemic stroke events separately in bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients after surgical aortic valve replacement for isolated severe aortic stenosis (AS). We prospectively enrolled 227 patients (n = 133 BAV and n = 94 TAV) with isolated severe AS scheduled for aortic valve replacement. A comprehensive intra- and inter-observer validated pre-operative echocardiogram with an analysis of LA reservoir strain was performed. Post-operative AF was defined as a sustained (>30 s) episode of AF or atrial flutter. The timing of neurological events was defined in accordance with the Valve Academic Research Consortium-3 criteria for stroke. Post-operative AF occurred in 114 of 227 patients (50.2%), with no difference between BAV and TAV patients (48.1 vs. 53.1%, P = 0.452). Persisting post-operative AF at discharge was more frequent in BAV patients (29.7 vs. 8.0%, P = 0.005). Pre-operative LA reservoir strain was independently associated with post-operative AF (odds ratio = 1.064, 95% confidence interval 1.032-1.095, P < 0.001), with a significant interaction between LA reservoir strain and aortic valve morphology (Pinteraction = 0.002). The cumulative transient ischemic attack (TIA)/stroke incidence during follow-up was significantly higher in BAV patients (19.1 vs. 5.8% at 5 years). Pre-operative LA function was associated with post-operative AF after aortic valve replacement in BAV AS patients, while post-operative AF in TAV AS patients likely depends on transient post-operative alterations and traditional cardiovascular risk factors. TIA/stroke during follow-up was more common in BAV AS patients.

Predictive machine learning models for ascending aortic dilatation in patients with bicuspid and tricuspid aortic valves undergoing cardiothoracic surgery: a prospective, single-centre and observational study

ObjectivesThe objective of this study was to develop clinical classifiers aiming to identify prevalent ascending aortic dilatation in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Design and...

Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease.

Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data. Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained. H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease. The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.

Transcatheter aortic valve replacement in the treatment of bicuspid aortic stenosis with "down-size" interventional valves: procedural and mid-term follow-up.

Due to the influence of anatomical structure, replacing the bicuspid valve using transcatheter aortic valve replacement (TAVR) would increase the risk of perivalvular leakage and conduction block, affecting the hemodynamic effect of the interventional valve. In this study, for bicuspid and tricuspid valves, we implemented different valve selection strategies to explore the safety and effectiveness of TAVR in the treatment of bicuspid aortic stenosis with "down-size" interventional valves using the VenusA-valve system. The operation was performed with the VenusA-valve via transfemoral approach. The selected valves were appropriately sized based on the results of transthoracic echocardiography (TTE), contrast-enhanced computed tomography (CT), and the morphology of intraoperative pre-dilation balloons. For tricuspid valve cases, the VenusA valve is usually larger than the annulus diameter, whereas the "down-size" approach was adopted for bicuspid aortic valve (BAV) cases. The shape of the pre-dilation balloon allowed further sizing of the annulus diameter by the degree of lumbar constriction of the balloon, aiding in intervention valve size selection, particularly in cases of BAVs. A total of 65 patients underwent TAVR for aortic stenosis with VenusA-valve systems. Of these, 29 cases had a BAV and 36 cases had a tricuspid aortic valve (TAV). The distribution of VenusA-valve sizes differed between TAV and BAV cases (P=0.007). Furthermore, there was a significant decrease in the average mean gradient in TAV patients from 54.7 to 12.2 mmHg (P<0.001), and in BAV patients from 61.6 to 14.3 mmHg (P<0.001). The percentage of paravalvular leakage greater than mild was 6.90% in the BAVs and 5.56% in the TAVs at procedural outcomes (P=0.955). The mean follow-up period was 22.23 months (range, 12 to 39 months). The proportion of New York Heart Association (NYHA) class III/IV decreased from 78.5% preoperatively to 11.3% at the last follow-up (P<0.001). A total of 27 patients with TAV and 19 patients with BAV underwent TTE at 1-year follow-up after operation. There was no significant contrast in the average pressure difference between TAVs and BAVs at 1-year follow-up (11.9 vs. 14.3 mmHg, P=0.18). The VenusA-valve for TAVR produced positive clinical outcomes and valve functionality in both BAVs and TAVs. In the case of BAVs, selecting a smaller interventional valve size was deemed viable.

Aortic Valve Repair with External Annuloplasty in Bicuspid versus Tricuspid Aortic Valve Patients.

Surgical repair for regurgitant bicuspid aortic valve (BAV) is promising but underutilized due to perceived complexities and lack of long-term data. This study evaluated the efficacy of valve-sparing root remodeling (VSRR) or isolated valve repair combined with calibrated external ring annuloplasty in BAV versus tricuspid aortic valve (TAV) patients. All patients operated on for aortic regurgitation and/or aneurysm at our institution between 2014 and 2022 were included and entered into the Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (AVIATOR). Patients with successful repair at index surgery (100% in the BAV group, 93% in the TAV group, p = 0.044) were included in a systemic follow-up with echocardiography at regular intervals. Among 132 patients, 58 were in the BAV (44%) and 74 in the TAV group (56%). There were no inter-group differences in preoperative patient characteristics, except BAV patients being significantly younger (47 ± 18 y vs. 60 ± 14 y, p < 0.001) and having narrower aortic roots at the level of sinuses (41 ± 6 mm vs. 46 ± 13 mm, p < 0.001) and sinotubular junctions (39 ± 10 mm vs. 42 ± 11, p = 0.032). No perioperative deaths were recorded. At four years, there was no significant difference in terms of overall survival (96.3% BAV vs. 97.2% TAV, p = 0.373), freedom from valve reintervention (85.2% BAV vs. 93.4% TAV, p = 0.905), and freedom from severe aortic regurgitation (94.1% BAV vs. 82.9% TAV, p = 0.222). Surgical repair of BAV combined with extra-aortic annuloplasty can be performed with low perioperative morbidity and mortality and excellent mid-term results which are comparable to TAV repair.

Ascending Aortic Progression After Isolated Aortic Valve Replacement Among Patients with Bicuspid and Tricuspid Aortic Valves.

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). 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. 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). 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.

The Prevalence of Coronary Artery Disease in Bicuspid Aortic Valve Patients: An Overview of the Literature.

The prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) patients is a debatable topic. Several studies have indicated that BAV patients have a lower prevalence of CAD compared with patients with a tricuspid aortic valve (TAV), but the effects of age and gender have not always been considered. This systematic review provides an overview of articles which report on CAD in BAV and TAV patients. Searches were executed in April 2021 and January 2022 according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines in three online databases: Medline, Embase, and Scopus. Screening and data extraction was done by two investigators separately. Primary and secondary outcomes were compared between BAV and TAV patients; a fixed effects model was used for correcting on confounders. Literature search yielded 1,529 articles with 44 being eligible for inclusion. BAV patients were younger (56.4 ± 8.3 years) than TAV patients (64 ± 10.3 years, p < 0.001). All CAD risk factors and CAD were more prevalent in TAV patients. No significant difference remained after correcting for age and gender as confounders. BAV patients have a lower prevalence of CAD and CAD risk factors compared with TAV patients. However, when the age differences between both groups are considered in the analyses, a similar prevalence of both CAD and CAD risk factors is found.

Analysis of Prevalence and Clinical Features of Aortic Stenosis in Patients with and without Bicuspid Aortic Valve Using Machine Learning Methods.

Aortic stenosis (AS) is the most commonly diagnosed valvular heart disease, and its prevalence increases with the aging of the general population. However, AS is often diagnosed at a severe stage, necessitating surgical treatment, due to its long asymptomatic period. The objective of this study was to analyze the frequency of AS in a population of cardiovascular patients using echocardiography (ECHO) and to identify clinical factors and features associated with these patient groups. We utilized machine learning methods to analyze 84,851 echocardiograms performed between 2010 and 2018 at the National Medical Research Center named after V.A. Almazov. The primary indications for ECHO were coronary artery disease (CAD) and hypertension (HP), accounting for 33.5% and 14.2% of the cases, respectively. The frequency of AS was found to be 13.26% among the patients (n = 11,252). Within our study, 1544 patients had a bicuspid aortic valve (BAV), while 83,316 patients had a tricuspid aortic valve (TAV). BAV patients were observed to be younger compared to TAV patients. AS was more prevalent in the BAV group (59%) compared to the TAV group (12%), with a p-value of <0.0001. By employing a machine learning algorithm, we randomly identified significant features present in AS patients, including age, hypertension (HP), aortic regurgitation (AR), ascending aortic dilatation (AscAD), and BAV. These findings could serve as additional indications for earlier observation and more frequent ECHO in specific patient groups for the earlier detection of developing AS.

Identification of immune-related signatures and pathogenesis differences between thoracic aortic aneurysm patients with bicuspid versus tricuspid valves via weighted gene co-expression network analysis.

Thoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients. Publically-available gene expression datasets, aortic tissue derived from TAA/BAV and TAA/TAV individuals, were analyzed by weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with those conditions. Gene Ontology (GO) enrichment analysis was performed on those modules to identify the enriched genes within those modules, which were verified by Gene Set Variation Analysis (GSVA) on a dataset derived from aortic smooth muscle cell gene expression between TAA/TAV and TAV/BAV patients. Immune cell infiltration patterns were then analyzed by CIBERSORT, and a protein-protein interaction (PPI) network was constructed based on WGCNA and enrichment analysis results to identify hub genes, followed by validation via stepwise regression analysis. Three signatures most strongly associated with TAA/TAV were confirmed by receiver operating characteristic (ROC) and decision curve analyses (DCA) between prior-established training and testing gene sets. WGCNA delineated 2 gene modules being associated with TAA/TAV vs. TAA/BAV; both were enriched for immune-associated genes, such as those relating to immune responses, etc., under enrichment analysis. TAA/TAV and TAA/BAV tissues also had differing infiltrating immune cell proportions, particularly with respect to dendritic, mast and CD4 memory T cells. Identified three signatures, CD86, integrin beta 2 (ITGB2) and alpha M (ITGAM), as yielding the strongest associations with TAA/TAV onset, which was verified by areas under the curve (AUC) at levels approximating 0.8 or above under ROC analysis, indicating their predictive value for TAA/TAV onset. However, we did not examine possible confounding variables, so there are many alternative explanations for this association. TAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments.

Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra. Aim Our study aims to compare TAVR outcomes in patients with BAV versus tricuspid aortic valves (TAV). A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane trials. Studies were included if they included BAV and TAV patients undergoing TAVR with quantitative data available for at least one of our predefined outcomes. Meta-analysis was performed by the random-effects model using Stata software. Fifty studies of 203,288 patients were included. BAV patients had increased 30-day all-cause mortality (odds ratio [OR] = 1.23 [1.00-1.50], p = 0.05), in-hospital stroke (OR = 1.39 [1.01-1.93], p = 0.05), in-hospital and 30-day PPI (OR = 1.13 [1.00-1.27], p = 0.04; OR = 1.16 [1.04-1.13], p = 0.01) and in-hospital, 30-day and 1-year aortic regurgitation (AR) (OR = 1.48 [1.19-1.83], p < 0.01; OR = 1.79 [1.26-2.52], p < 0.01; OR = 1.64 [1.03-2.60], p = 0.04). Subgroup analysis on new-generation valves showed a reduced 1-year all-cause mortality (OR = 0.86 [CI = 0.75-0.98], p = 0.03), despite higher in-hospital and 30-day PPI (OR = 0.1.21 [1.04-1.41], p = 0.01; OR = 1.17 [1.05-1.31], p = 0.01) and in-hospital AR (OR = 1.62 [1.14-2.31], p = 0.01) in the BAV group. The quality of included studies was moderate-to-high, and only three analyses presented high heterogeneity. TAVR is associated with comparable outcomes in patients with BAV and TAV. Careful selection of BAV cases by preprocedural assessment of valve anatomy and burden of calcification, pre- and post-procedural dilation, and implementing newer generations of valves may improve the safety and efficacy of TAVR in BAV patients.