Bicuspid Aortic Valve Research Articles

Malposition of the Aortic Valve After TAVI with Consequent Severe Aortic Regurgitation

Male, 63 years old, with a long-term history of ischemic heart disease. After an myocardial infarction 20 years ago, a surgical evascularization was performed with left interior mammary artery (LIMA) – left anterior descending (LAD) bypass. Elective percutaneous coronary intervention (PCI) with the implantation of one bare metal stent in the circumfl ex artery was done 4 years ago. During this procedure, an indication for transcatheter aortic valve implantation (TAVI) was set due to the progression of stenosis gradient in the bicuspid aortic valve. Immediately after the TAVI procedure, the patient developed symptoms and signs of acute heart failure due to the malposition of the aortic valve and consequent severe aortic regurgitation (AR)(1). The images depict a transesophageal echocardiographic examination after TAVI (Figure 1-4). Severe AR with paravalvular jets is the result of the malposition of the biological valve after TAVI, where the valve partially occupies the left ventricular outfl ow tract. The inadequately positioned aortic val-ve was surgically removed, followed by the implantation of a mechanical aortic valve. Subsequently, as the patient was dependent on a temporary pacemaker, a permanent dual-chamber pacemaker was implanted. Following the surgical treatment, the patient recovered successfully (2,3).

Pro-angiogenic cytokine features of left ventricular remodeling in patients with bicuspid aortic valve

ObjectiveBicuspid 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. MethodsFrom 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. ResultsAmong 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). ConclusionDecreased 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.

Transcatheter aortic valve replacement in China - a review of the available evidence.

This paper discusses aortic stenosis (AS) in China, emphasising the role of transcatheter aortic valve replacement (TAVR) in treating AS in an ageing population. AS characteristics, its treatment and the clinical outcomes of transfemoral TAVR in Chinese patients are described via a systematic review. AS affects >1% of the Chinese population aged ≥65 years, with degenerative AS predominating over rheumatic AS among this age group. Chinese patients often have high aortic valve (AV) calcification with bicuspid AV morphology. In 2021, 38,000 surgical aortic valve replacements (SAVR) were reported in China, while the number of TAVR increased from 293 in 2017 to 7,357 in 2021. There are four self-expanding valves and one balloon-expandable SAPIEN 3 valve available in China. Among them, the Venus A-Valve is the most studied and widely used, whereas limited data are available for VitaFlow, TaurusOne, and SAPIEN 3. Notably, 10.0-16.5% of Venus A-Valve recipients and 0.2% of SAPIEN 3 recipients required multiple valve implantations. The rates of 30-day paravalvular leakage were 0-11.7%/0% for Venus A-Valve, 2.0%/0% for VitaFlow, and 0%/0% for SAPIEN 3, for moderate and severe leakage, respectively. Thirty-day all-cause mortality rates were 3.7-10.0% for Venus A-Valve, 0.9% for VitaFlow, and 0-3.2% for SAPIEN 3. One-year all-cause mortality rates were 5.9-13.6% for Venus A-Valve, 0-4.5% for VitaFlow, 6.7% for TaurusOne, and 6.2% for SAPIEN 3. The Venus A-Valve indicated lower 30-day permanent pacemaker implantation (PPI) rates (7.4-20.5%) than VitaFlow and TaurusOne. Outcomes for patients with bicuspid or tricuspid aortic valves were similar. AS is rising among the elderly Chinese population; SAVR is common, and TAVR is increasing. Limited device comparisons exist, but the Venus A-Valve seems to have lower PPI rates, and SAPIEN 3 has low 30-day mortality in China.

Patients with a Bicuspid Aortic Valve (BAV) Diagnosed with ECG-Gated Cardiac Multislice Computed Tomography-Analysis of the Reasons for Referral, Classification of Morphological Phenotypes, Co-Occurring Cardiovascular Abnormalities, and Coronary Artery Stenosis.

Background/Objectives: The aim of this study was to analyze a group of patients with a bicuspid aortic valve (BAV) examined with ECG-gated cardiac CT (ECG-CT), focusing on the assessment of the clinical reasons for cardiac CT, cardiovascular abnormalities coexisting with their BAV, and coronary artery stenosis. Methods: A detailed statistical analysis was conducted on 700 patients with a BAV from a group of 15,670 patients examined with ECG-CT. Results: The incidence of a BAV in ECG-CT was 4.6%. The most common reason for examination was suspicion of coronary heart disease-31.1%. Cardiovascular defects most frequently associated with a BAV were a VSD (4.3%) and coarctation of the aorta (3.6%), while among coronary anomalies, they were high-take-off coronary arteries (6.4%) and paracommissural orifice of coronary arteries (4.4%). The analysis of the coronary artery calcium index showed significantly lower values for type 2 BAV compared to other valve types (p < 0.001), with the lowest average age in this group of patients. Moreover, the presence of a raphe between the coronary and non-coronary cusps was associated with a higher rate of significant coronary stenosis compared to other types of BAVs (p < 0.001). Conclusions: The most common reason for referral for cardiac ECG-CT in the group ≤ 40-year-olds with a BAV was the suspicion of congenital cardiovascular defects, while in the group of over 40-year-olds, it was the suspicion of coronary artery disease. The incidence of cardiovascular abnormalities co-occurring with BAV and diagnosed with ECG-CT differs among specific patient subgroups. The presence of a raphe between the coronary and non-coronary cusps appears to be a potential risk factor for significant coronary stenosis in patients with BAVs.

Evaluation of Both Aortic Diameters (Annulus, Sinus of Valsalva, Ascending Aorta) and Z-Scores in Patients with Bicuspid Aortic Valve, Aortic Valve Prolapse, and Mitral Valve Prolapse

Evaluation of Both Aortic Diameters (Annulus, Sinus of Valsalva, Ascending Aorta) and Z-Scores in Patients with Bicuspid Aortic Valve, Aortic Valve Prolapse, and Mitral Valve Prolapse

Mid-Term Outcomes of Aortic Valve Repair Without Aortic Root Replacement: A Single-Center Experience.

Background Aortic valve (AV) repair is a challenging procedure due to its complexity, lower reproducibility, and steep learning curve. To examine its durability and validity, we investigated mid-term outcomes following AV repair without aortic root replacement. Methods Between March 2007 and May 2018, we retrospectively identified 14 patients who underwent AV repair without aortic root replacement at our institution. We investigated their baseline characteristics and postoperative outcomes, including the reoperation rate due to aortic regurgitation (AR) recurrence. Furthermore, we divided them into two groups: those who required reoperation due to AR recurrence (Group R) and those who did not require reoperation (Group F), and statistically compared them. Results The median age was 52.5 years (IQR: 42.0-60.8), with 11 male patients (78.6%). Eight patients (57.1%) had a bicuspid AV. Five cases (35.7%) underwent reoperation due to AR recurrence during a median follow-up period of 5.5 years. There were no significant differences in baseline characteristics between Group R (n=5, 35.7%) and Group F (n=9, 64.3%), including AR etiology, AV repair procedure, and intraoperative AR grade after the final declamp. All cases in Group R had at least mild to moderate AR on the echocardiogram before discharge. Regarding the AR grade before discharge, Group R had a significantly higher grade than Group F (p = 0.013). Conclusions The indication for AV repair for AR might need to be reassessed due to the considerable mid-term reoperation rate. Cases of AV repair with more than mild AR at discharge should be carefully monitored, as they are likely to require future reoperation for AR.

Massive sinus of Valsalva aneurysm with an associated bicuspid aortic valve: A rare clinical image

Abstract A sinus of Valsalva aneurysm is a rare cardiac anomaly characterized by an abnormal dilatation of the aortic root. This occurs due to a weakened elastic lamina at the junction of the aortic media and the annulus fibrosus. The aneurysm can be congenital or acquired and comprises up to 3.5% of all congenital cardiac defects. Due to the aneurysm’s physiologic function and location, it can present significant clinical consequences in both the rupture and unruptured state. We present the case of a middle-aged male with no significant medical history who was found to have a massive unruptured sinus of Valsalva aneurysm. He was treated surgically with no postoperative complications.

Bicuspid Aortic Valve Disease with Early-Onset Complications: Characteristics and Aortic Outcomes

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults, but it can also cause childhood-onset complications. The presentation and clinical course of young adults who present due to BAV complications are relatively uncharacterized. In a multicenter study, we found that young people who experience significant complications related to BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early-onset BAV complications.

Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

ORTHOTOPIC HEART TRANSPLANTATION IN A PATIENT WITH A PERSISTENT LEFT SUPERIOR VENA CAVA: СASE REPORT

Introduction. Persistent left superior vena cava is the most common congenital venous abnormality of the thorax and has a prevalence of 0,3-0,5% among the general population. In most cases, the presence of a persistent left superior vena cava is asymptomatic and is usually a finding during surgery. Most often additional left superior vena cava coexists with superior vena cava in 80-90% cases. This feature is extremely important for choosing the optimal surgical tactics. Case Presentation. Patient Sh., 44 years old, was urgently hospitalized for orthotopic heart transplantation. From the anamnesis it is known that in 2017 the patient was diagnosed congenital heart disease: critical stenosis of the bicuspid aortic valve. However, the patient refused surgery at that moment. Conservative treatment was carried out. In 2022, the patient`s condition progressively worsened: severe exertional dyspnea, increased shortness of breath at rest, pitting edema in the lower extremities, interruptions in the work of the heart. The patient is diagnosed: dilated cardiomyopathy. The patient was included in the waiting list on the heart transplantation. In March 2023, patient underwent orthotopic heart transplantation with reconstruction a persistent left superior vena cava. A tubular conduit from the autopericardium with a diameter of 20 mm and a length of 5 cm was used for reconstruction. An anastomosis was formed between the distal part of the accessory left superior vena cava and the right atrial auricle. The patient was discharged without any complications and no signs of venous congestion in the upper body were detected during the follow-up examination after three months of observation. Conclusions. Our clinical observation demonstrates the feasibility of successful orthotopic heart transplantation using an autologous autopericardium graft in patients with a persistent left superior vena cava and shows encouraging immediate follow-up results.

Patient-specific bicuspid aortic valve hemodynamics study based on computer simulation and in vitro experiment

Patient-specific bicuspid aortic valve hemodynamics study based on computer simulation and in vitro experiment

Computational study of transcatheter aortic valve replacement based on patient-specific models-rapid surgical planning for self-expanding valves.

Transcatheter aortic valve replacement (TAVR) is a minimally invasive interventional solution for treating aortic stenosis. The complex post-TAVR complications are associated with the type of valve implanted and the position of the implantation. The study aimed to establish a rapid numerical research method for TAVR to assess the performance differences of self-expanding valves released at various positions. It also aimed to calculate the risks of postoperative paravalvular leak and atrioventricular conduction block, comparing these risks to clinical outcomes to verify the method's effectiveness and accuracy. Based on medical images, six cases were established, including the aortic wall, native valve and calcification; one with a bicuspid aortic valve and five with tricuspid aortic valves. The parameters for the stent materials used by the patients were customized. High strain in the contact area between the stent and the valve annulus may lead to atrioventricular conduction block. Postoperatively, the self-expanding valve maintained a circular cross-section, reducing the risk of paravalvular leak and demonstrating favorable hemodynamic characteristics, consistent with clinical observations. The outcomes of the six simulations showed no significant difference in valve frame morphology or paravalvular leak risk compared to clinical results, thereby validating the numerical simulation process proposed for quickly selecting valve models and optimal release positions, aiding in TAVR preoperative planning based on patients'geometric characteristics.

Valve-Sparing Aortic Root Replacement in Children and Adolescents: Experience and Outcomes in a Public Institution in Argentina

Background: Valve-sparing aortic root replacement (VSARR) with reimplantation technique is indicated in patients with aortic root aneurysm. We evaluated the mid-term outcomes of this surgical technique in children and adolescents in our institution. Methods: Retrospective study. Twenty-one patients who underwent VSARR surgery were included between July 2006 and July 2022. The relationship between baseline variables and progression of aortic regurgitation (AR) was assessed. Results: The median age was 13 years. Seventeen patients had connective tissue disorders (3 with bicuspid aortic valve), 2 operated congenital heart disease, 1 isolated bicuspid aortic valve and 1 Turner syndrome. Thirteen patients had mild AR and 5 had moderate AR preoperatively. Three patients underwent early aortic replacement, 2 due to endocarditis and 1 due to severe acute AR. The median follow-up was 4.1 years. Of 17 patients at follow-up, 2 developed mild-moderate AR, 2 moderate AR and 3 severe AR. One of them underwent Bentall surgery. No association was found between the degree of preoperative AR or the presence of bicuspid aortic valve and the progression of postoperative AR. There was no association between the type of postoperative valve coaptation and the development of AR greater than mild at follow-up. Conclusions: VSARR with reimplantation is a feasible surgical technique with favorable mid-term outcomes and low reoperation rate in pediatric patients.

High Lp(a) levels are a potential risk factor for aortic valve interventions in patients with bicuspid aortic valve

High Lp(a) levels are a potential risk factor for aortic valve interventions in patients with bicuspid aortic valve

Interrupted aortic arch with bicuspid aortic valve stenosis in an adult: A case report.

The case report describes a rare instance of an interrupted aortic arch (IAA) with bicuspid aortic valve stenosis in a 48-year-old male patient with a one-year history of refractory hypertension, chest pain, and numbness in the upper and lower extremities. A single-stage operation was performed through a midline sternotomy, involving aortic valve replacement and posterior pericardial ascending-to-descending aortic bypass. Managing such rare conditions can be challenging due to limited guidelines, no meaningful conclusion may be made as to whether single-stage or two-stage repair is superior. Final management decision in adult patients with IAA must be individualized and depend on the associated malformations, patient preference, and precise anatomy imaging. The single-stage posterior pericardial ascending-to-descending aortic bypass appears as a safe surgical method in such cases when concomitant cardiac procedures are indicated.

TAVR with self- expandable valves: what challenges in bicuspid aortic valve disease?

Background: The bicuspid aortic valve (BAV) represents a complex anatomic entity for transcatheter aortic valve replacement (TAVR) because of its unique technical challenges. All the randomized clinical trials comparing outcomes of TAVI with surgery till date, have excluded patients with bicuspid aortic valve. The only data in literature come from empirical observations, with large variability in implantation techniques across different centers and operators. Objective: These case reports describe the results of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve stenosis (BAV) using self-expandable valves with their clinical, imaging, procedural, and follow-up settings. Case reports: We report 3 cases of TAVR with BAV. The patients were at high risk of surgery. Baseline cardiac computed tomography (CT) was analyzed by interventional cardiologists. We used self-expandable valves in all the procedures. There were no cases of valve embolization or need for a second valve, no post-dilatation, no cases of moderate or severe aortic regurgitation, and none of the cases required a permanent pacemaker implantation. Conclusion: With the available observational data, it seems that TAVI is indeed technically feasible in selected BAV patients with acceptable results. Self-expandable valves can be safe and effective devices for these procedures. Most of the current data studies highlight the importance of preprocedural imaging determining the outcome of TAVI in BAV patients. Advancements device iterations and procedural refinements will continue to improve the outcomes of these patients treated by TAVR.

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&amp;gt;2 and p-value &amp;lt;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.

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 &amp;lt;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.

Connecting the dots: molecular pathways in bicuspid aortopathy explored

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Junta de Andalucía, Ministerio de Ciencia e Innovación Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. It predisposes to thoracic aortic dilatation (TAD), aneurysm and dissection. The current consensus is that the genetic defect that leads to the aortic valve malformation also causes structural anomalies of the ascending aorta. Altered hemodynamics caused by the abnormal valve morphology would accelerate aortic media degeneration. Molecular markers and pathways involved in the aetiology and pathophysiology of bicuspid aortopathy are poorly understood. Objective To elucidate the molecular and cellular mechanisms of the disease and to identify potential predictive molecular markers using a well-established isogenic hamster model (T strain) with a high (∼40%) incidence of BAV TAD. Methods Comparative quantitative proteomics combined with Western blot and morpho-molecular analyses in the ascending aorta of tricuspid aortic valve (TAV) and BAV animals from the T strain and TAV animals from a control strain. This strategy allows exploring independently the genetic and hemodynamic effects on the aorta in genetically homogeneous populations. Results The major molecular defect in the aorta of genetically homogeneous BAV individuals is PI3K/AKT overactivation caused by alterations in the EGF, ANGII and TGF-β signalling pathways. PI3K/AKT affects the downstream eNOS, MAP2K1/2, NF-κB, mTOR and WNT pathways. Most of these alterations are seen in independent patient studies with different clinical presentations, but not in TAV hamsters from the T strain, which mainly show downregulation of the WNT pathway. Conclusions We identify a combination of defective interconnected molecular pathways, directly linked to the central PI3K/AKT pathway, common to both BAV-associated TAD patients and hamsters. The defects indicate a shift of smooth muscle cells towards the synthetic phenotype induced by endothelial-to-mesenchymal transition, oxidative stress and inflammation. WNT signalling represents a genetic factor that may cause aortic structural abnormalities and aneurysm predisposition, whereas hemodynamics is the main trigger of molecular changes, likely determining the progression of aortopathy. We identify twenty-seven novel potential biomarkers with high predictive value.

Machine Learning Analysis of Facial Photographs for Predicting Bicuspid Aortic Valve

Machine Learning Analysis of Facial Photographs for Predicting Bicuspid Aortic Valve