Presence Of Bicuspid Aortic Valve Research Articles

Aortic stenosis assessment from the 3-chamber cine: Ratio of balanced steady-state-free-precession (bSSFP) blood signal between the aorta and left ventricle predicts severity.

Cardiovascular magnetic resonance (CMR) imaging is an important tool for evaluating the severity of aortic stenosis (AS), co-existing aortic disease, and concurrent myocardial abnormalities. Acquiring this additional information requires protocol adaptations and additional scanner time, but is not necessary for the majority of patients who do not have AS. We observed that the relative signal intensity of blood in the ascending aorta on a balanced steady state free precession (bSSFP) 3-chamber cine was often reduced in those with significant aortic stenosis. We investigated whether this effect could be quantified and used to predict AS severity in comparison to existing gold-standard measurements. Multi-centre, multi-vendor retrospective analysis of patients with AS undergoing CMR and transthoracic echocardiography (TTE). Blood signal intensity was measured in a ∼1cm2 region of interest (ROI) in the aorta and left ventricle (LV) in the 3-chamber bSSFP cine. Because signal intensity varied across patients and scanner vendors, a ratio of the mean signal intensity in the aorta ROI to the LV ROI (Ao:LV) was used. This ratio was compared using Pearson correlations against TTE parameters of AS severity: aortic valve peak velocity, mean pressure gradient and the dimensionless index. The study also assessed whether field strength (1.5T vs. 3T) and patient characteristics (presence of bicuspid aortic valves (BAV), dilated aortic root and low flow states) altered this signal relationship. 314 patients (median age 69 [IQR 57-77], 64% male) who had undergone both CMR and TTE were studied; 84 had severe AS, 78 had moderate AS, 66 had mild AS and 86 without AS were studied as a comparator group. The median time between CMR and TTE was 12 weeks (IQR 4-26). The Ao:LV ratio at 1.5T strongly correlated with peak velocity (r=-0.796, p=0.001), peak gradient (r=-0.772, p=0.001) and dimensionless index (r=0.743, p=0.001). An Ao:LV ratio of <0.86 was 84% sensitive and 82% specific for detecting AS of any severity and a ratio of 0.58 was 83% sensitive and 92% specific for severe AS. The ability of Ao:LV ratio to predict AS severity remained for patients with bicuspid aortic valves, dilated aortic root or low indexed stroke volume. The relationship between Ao:LV ratio and AS severity was weaker at 3T. The Ao:LV ratio, derived from bSSFP 3-chamber cine images, shows a good correlation with existing measures of AS severity. It demonstrates utility at 1.5T and offers an easily calculable metric that can be used at the time of scanning or automated to identify on an adaptive basis which patients benefit from dedicated imaging to assess which patients should have additional sequences to assess AS.

Abstract 14180: A Case of Symptomatic Thoracic Aortic Aneurysm After Recent Fluoroquinolone Use

Background: Thoracic aortic aneurysms (TAAs) can be found in 1-2/1000 individuals in the general population and are commonly associated with genetic disorders of connective tissue and bicuspid aortic valve (BAV). Larger size, distal aneurysms, high DBP and presence of BAV are some factors that can accelerate aneurysm growth. Case: A 37-year-old male without a history of recent trauma or stimulant use presented to the emergency room with 2 days of chest tightness. He had acute worsening overnight and awoke with chest pain, discomfort in the suprasternal notch and between the shoulder blades. He had no other medical history, however, was treated with a 10-day course of Ciprofloxacin for epididymitis 3 weeks prior. On presentation, the patient had active pleuritic chest pain, tachycardia and tachypnea with no abnormalities on cardiac auscultation. EKG showed sinus tachycardia, PVCs, and nonspecific ST elevations in leads II, III and aVF with normal troponins and chest X-ray. CT chest angiogram revealed a 60 mm ascending aortic aneurysm ( Fig. 1a ). Doming of the right cusp of the aortic valve in the parasternal view ( Fig. 1b ) raised suspicion for BAV which was confirmed with the classic fish mouth appearance on the TEE ( Fig. 1c ). The patient underwent successful aortic repair with graft placement. First degree relatives were offered screening for BAV. Ciprofloxacin was replaced with Sulfamethoxazole-Trimethoprim for treating his residual epididymal infection. Discussion: TAA rupture is associated with a &gt;90% mortality rate. It is important to be aware of echocardiographic features of BAV as this can predispose to accelerated aneurysm growth. Additionally, fluoroquinolones (FQs) are a commonly prescribed class of antibiotics that may affect the structural integrity of the aorta, associated with aneurysm enlargement and rupture. This case offers an important example to highlight why the FDA recommends against the use of FQs in patients with known TAA or risk factors for it.

Assessing turbulent effects in ascending aorta in presence of bicuspid aortic valve

Aortic valves with bicuspids have two rather than three leaflets, which is a congenital heart condition. About 0.5–2% of people have a bicuspid aortic valve. Blood flow through the aorta is commonly believed to be laminar, although aortic valve disorders can cause turbulent transitions. Understanding the impact of turbulence is crucial for foreseeing how the disease will progress. The study’s objective was use large eddy simulation to provide a thorough analysis of the turbulence in bicuspid aortic valve dysfunction. Using a large eddy simulation, the blood flow patterns of the bicuspid and tricuspid aortic valves were compared, and significant discrepancies were found. The velocity field in flow in bicuspid configurations was asymmetrically distributed toward the ascending aorta. In tricuspid aortic valve (TAV) the flow, on the other hand, was symmetrical within the same aortic segment. Moreover, we looked into standard deviation, Q-criterion, viscosity ratio and wall shear stresses for each cases to understand transition to turbulence. Our findings indicate that in the bicuspid aortic valve (BAV) case, the fluid-dynamic abnormalities increase. The global turbulent kinetic energy and time-averaged wall shear stress for the TAV and BAV scenarios were also examined. We discovered that the global turbulent kinetic energy was higher in the BAV case compared to TAV, in addition to the increased wall shear stress induced by the BAV in the ascending aorta.

Fifteen-Year Outcomes After Valve-Sparing Aortic Root Remodelling or Exclusion of the Non-Coronary Sinus: When to Preserve the Sinuses of Valsalva?

Isolated exclusion of the non-coronary sinus (NCS) is an attractive strategy in valve-sparing aortic root surgery, which avoids the mobilisation and re-implantation of coronary ostia. However, the long-term durability of aortic valve repair and the fate of remnant sinuses of Valsalva remain unclear. From January 2006 to December 2013, 29 patients underwent replacement of the ascending aorta extending to the NCS (group NCS) and 56 patients underwent a modified Yacoub procedure (group MY) in our centre by a single surgeon. Significant difference of preoperative parameters was observed between two groups in the presence of bicuspid aortic valve (41.4% vs 12.5%, p=0.002) and the diameter of the sinus of Valsalva (47.3±4.7 mm vs 51.5±4.9 mm, p=0.01). The group NCS, as compared to the group MY, was associated with significantly shorter cardiopulmonary bypass time (106.6±40.5 min vs 138.4±37.5 min, p=0.001) and aortic cross clamping time (69.0±21.8 min vs 105.4±27.8 min, p<0.01). The mean follow-up was 11.5±2.8 years. No surgical re-intervention was performed for aortopathies of the aortic root; the neo-sinus were not dilated in either groups (38.2±4.2 mm vs 34.0±4.0 mm, p<0.01). The 10-year freedom from aortic valve-related re-operation was estimated to be 96.6±3.4% and 94.5±3.1% (p=0.58), and the cumulative 10-year survival rates were 95.2±4.6% and 85.6±4.7% (p=0.61) in the group NCS and the group MY, respectively. Aortic valve-sparing isolated NCS replacement can be safely performed in selected patients; its early outcomes, overall survival and long-term freedom from aortic valve-related or aortopathy-related re-intervention were comparable to those obtained with the Yacoub procedure.

The role of 4-dimensional flow in the assessment of bicuspid aortic valve and its valvulo-aortopathies.

Bicuspid aortic valve is the most common congenital cardiac malformation and the leading cause of aortopathy and aortic stenosis in younger patients. Aortic wall remodelling secondary to altered haemodynamic flow patterns, changes in peak velocity, and wall shear stress may be implicated in the development of aortopathy in the presence of bicuspid aortic valve and dysfunction. Assessment of these parameters as potential predictors of disease severity and progression is thus desirable. The anatomic and functional information acquired from 4D flow MRI can allow simultaneous visualisation and quantification of the pathological geometric and haemodynamic changes of the aorta. We review the current clinical utility of haemodynamic quantities including velocity, wall sheer stress and energy losses, as well as visual descriptors such as vorticity and helicity, and flow direction in assessing the aortic valve and associated aortopathies.

Aortic dilation and growth in women with Turner syndrome

ObjectiveWomen with Turner syndrome (TS) are at increased risk of aortic dissection, which is a life-threatening event associated with aortic dilation. Knowledge on the development of aortic dilation over time...

Etiology, Risk Factors and Clinical Outcomes in Infective Endocarditis Patients Requiring Cardiac Surgery.

Background: Infective endocarditis, which may be caused by various microbial agents, severely affects the innermost layer of the heart and often leads to poor clinical outcomes. The purpose of this study was to investigate the etiology, risk factors and short and long-term outcomes of infective endocarditis caused by various bacterial agents in patients requiring cardiac surgery. Methods: One hundred and forty-four patients aged 18 years or above with indications for cardiac surgery due to S. aureus, Streptococcus spp., E. faecalis or coagulase-negative staphylococci caused infective endocarditis were included in this study. Results: S. aureus, Streptococcus spp., E. faecalis and coagulase-negative staphylococci were the causative agents of infective endocarditis in 44 (30.6%), 35 (24.3%), 33 (22.9%) and 32 (22.2%) patients, respectively. The presence of bicuspid aortic valve was the most common predisposing factor confirmed in 19 (23.5%), whereas intravenous drug usage was the most common in 17 (11.8%) patients. No significant differences in intrahospital mortality due to infective endocarditis caused by various bacterial agents were found, however, the worsening of long-term prognosis of endocarditis caused by S. aureus when compared to E. faecalis was confirmed (p = 0.03). The presence of S. aureus was associated with significantly higher rates of embolic complications (p = 0.003). The presence of coagulase-negative staphylococci was associated with prosthetic valve endocarditis (p = 0.015) and perivalvular complications (p = 0.024). Conclusions: In contrast to E. faecalis, the presence of S. aureus determines the worsening of the long-term mortality from infective endocarditis. Perivalvular complications are associated with the presence of coagulase-negative staphylococci.

Late complication rates after aortic coarctation repair in patients with or without a bicuspid aortic valve

ObjectivePatients with previously repaired aortic coarctation (CoA) are at risk of developing late surgical complications. Many patients with CoA also have a bicuspid aortic valve (BAV). We sought to determine...

Prevalence and progression of aortic dilatation in adult patients with Turner syndrome: a cohort study.

Turner syndrome (TS) is a rare disorder affecting 1/2500 female newborn. Aortic dilatation (AD) and aortic dissection represent a major concern in TS. The aims of our study were to describe the aortic root growth, potential aortic dilatation (AD) risk factors and cardiovascular outcomes in a cohort of patients with TS. Among 204 adult patients included, 197 were studied using a standardized 1.5 Tesla MRI protocol. AD was defined as an aortic diameter ≥20 mm/m2 at the Valsalva sinuses and/or at the ascending aorta, when indexed to body surface area. At baseline, AD was present in 81/197 (41.1%) and 32/197 (16.2%) of patients, at the levels of Valsalva and ascending aorta, respectively. The aortic Valsalva diameter was larger in patients treated for thyroiditis (P < 0.001). Potential risk factors of AD were aging (P < 0.001) and the presence of bicuspid aortic valve (BAV) (P = 0.002). The hazard ratio (HR) of AD occurrence in the presence of BAV was 2.2 (95% CI: 1.33-3.71). After a median follow-up period of 5.1 years (n = 143), AD was present in 58/143 (40.6%) and 25/143 (17.5%) of patients at the levels of Valsalva and ascending aorta, respectively. The median aortic growth of the Valsalva sinuses remained stable. At the ascending aorta, it increased by 0.14 ± 0.61 mm/year. Only one aortic-related death was observed. AD is common in adult patients with TS. However, our results are rather reassuring, as the median aortic diameters remained stable after 5.1 years and few aortic events were observed.

Clinical significance of family history and bicuspid aortic valve in children and young adult patients with Marfan syndrome.

Marfan syndrome is an autosomal dominant disorder of the connective tissue, whose cardinal features affect eyes, musculoskeletal, and cardiovascular system. Despite prevalence and natural history of cardiovascular manifestation are well known in adults, little is known about children and young adult patients. The aim of this study was to describe a well-characterised cohort of consecutive children and young patients with marfan syndrome, looking at the impact of family history and presence of bicuspid aortic valve on disease severity. A total of 30 consecutive children and young patients with Marfan syndrome were evaluated. All patients underwent a comprehensive clinical-instrumental-genetic evaluation. Particular attention was posed to identify differences in prevalence of cardiovascular abnormalities between patients with and without family history of Marfan syndrome or bicuspid aortic valve. Of these 30 patients, family history of Marfan syndrome and bicuspid aortic valve were present in 76 and 13%, respectively. Compared to patients with family history of Marfan syndrome, those without showed higher prevalence of aortic sinus dilation (87 versus 32%, p-value = 0.009), greater aortic sinus diameters (4.2 ± 2.1 versus 1.9 ± 1.1 z score, p-value = 0.002), and higher rate of aortic surgery during follow-up (37 versus 0%, p-value = 0.002). Compared to patients with tricuspid aortic valve, those with bicuspid aortic valve were younger (3.2 ± 4.3 versus 10.7 ± 6.8 years old, p-value = 0.043), showed greater aortic sinus diameters (4.2 ± 0.9 versus 2.2 ± 1.6 z score, p-value = 0.033), and underwent more frequently aortic root replacement (50 versus 4%, p-value = 0.004). In our cohort of patients with Marfan syndrome, the absence of family history and the presence of bicuspid aortic valve were associated to severe aortic phenotype and worse prognosis.

P1774 Myocardial work indices in adult patients with repaired aortic coartation

Abstract Background Myocardial strain analysis is a tool that allows a more precise assessment of cardiac performance. However, strain is relatively load dependent. New tools have been developed, with afterload adjustment. It was our objective to assess myocardial work (MW) in patients with repaired aortic coartation (ACo). Methods Study of consecutive adult patients with corrected ACo submitted to a routine transthoracic echocardiogram in 2018 at our centre. Patients with an aortic valve prosthesis, more than mild aortic stenosis / regurgitation, with pacemakers, with other non-corrected congenital heart diseases (with the exception of bicuspid aortic valve) were excluded from the analysis. A semi-automated strain analysis was performed with speckle tracking technology and both global longitudinal strain (GLS) and MW were estimated using GE software™. Blood pressure was simultaneously measured in the patient’s right arm. We specifically assessed: Global Work Index (GWI), Global Constructive Work (GCW), Global Work Waste (GWW) and Global Work Efficiency (GWE) Results Twenty patients were included in the study, mean age of 36 ± 9 years, 30% males. Mean body surface area was 1.7. In this group of patients, 40% were hypertensives and in 55% there was a concomitant bicuspid aortic valve. Mean maximum aortic valve gradient was 11 mmHg and mean descending aortic gradient was 19 mmHg. Compared to recently published reference values for a normal population, repaired ACo patients had lower values of MW (Table). In multivariate linear regression analysis, independent predictors of GWI are systolic blood pressure (β=0.441) and let atrial volume indexed (LAVI) (β=0.507). For GCW, male gender (β=-0.605), LAVI (β=0.530) and diastolic blood pressure (β=-0.742). For GWE, the only predictor was LAVI (β=0.498) and no predictor was identified for GWW. The presence of bicuspid aortic valve, aortic valve gradient and descending aortic gradient did not have any influence in MW parameters, although higher aortic valve gradients were excluded from this study. Conclusion Adult patients with repaired ACo, present lower MW indices and the main determinant for that difference are LAVI and blood pressure. GWW is the most independent parameter. Results Variable Reference population n = 226 Patients with repaired ACo n = 20 p-value GWI (mmHg%) 1896 ± 308 1782 ± 389 &amp;lt;0.001 GCW (mmHg%) 2232 ± 331 2154 ± 390 &amp;lt;0.001 GWW (mmHg%) 78 (53-122) 76 (56-197) &amp;lt;0.001 GWE (mmHg%) 96 (94-97) 95 (91-97) &amp;lt;0.001

Low and Oscillatory Wall Shear Stress Is Not Related to Aortic Dilation in Patients With Bicuspid Aortic Valve: A Time-Resolved 3-Dimensional Phase-Contrast Magnetic Resonance Imaging Study.

To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence. Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.

Cardiovascular magnetic resonance imaging characteristics and influence factors of aortic insufficiency patients with myocardial fibrosis

Objective: To investigate the cardiovascular magnetic resonance (CMR) imaging characteristics and influence factors of aortic insufficiency (AI) patients with myocardial fibrosis. Method: This retrospective study included 59 AI patients who received CMR and transthoracic echocardiography (TTE) examinations from June 2011 to February 2015. AI patients were divided into 2 groups: bicuspid aortic valve (BAV) group (n=30) and non-BAV group (n=29). Patients were also divided into late gadolinium enhancement (LGE) group (n=27) and non-LGE group (n=32). The baseline clinical characteristics were collected through electronic medical records. Hemodynamic parameters such as grade of AI, cardiac functional parameters and LGE mass fraction (LGE%) were measured by CMR post-processing analysis. Kappa test was used to assess the consistency of AI severity between CMR and TTE, and the multivariate logistic regression analysis was performed to evaluate influence factors of myocardial fibrosis in AI patients. Results: (1) 56 (94.9%) patients were male, and the mean age was (44.2±11.0) years old. There was no significant difference in age and gender, hypertension, hyperlipidemia, alcoholic consumption between BAV and non-BAV group (all P>0.05). There were a higher proportion of smoking history (P=0.008), a lower body mass index (BMI) (P=0.020) in the LGE group than in the non-LGE group. (2) The accuracy of CMR in diagnosis of BAV was 96.7% (29/30) compared to the gold standard. In the BAV group, 20 patients (66.7%) were with fusion of left and right cusp (L-R), 5 patients (16.7%) were with fusion of right and noncoronary cusp (R-N), 5 patients (16.7%) were with fusion of left and noncoronary cusp (L-N); patients with BAV had larger left ventricular end diastolic volume index (LVEDVi), left ventricular end systolic volume index (LVESVi), higher proportion of LGE and lower left ventricular ejection fraction (LVEF) than those in non-BAV group (all P<0.05). There were 19 patients with BAV in the LGE group, the cases of L-R, R-N, L-N were 10 (52.6%), 5 (26.3%), and 4 (21.1%), respectively. In the non-LGE group, patients with BAV of L-R, R-N, L-N were 10 (90.9%), 0, and 1 (9.1%), respectively. Patients with LGE had lower body surface area (BSA), LVEF and larger LVEDVi, LVESVi, left ventricular mass index (LVMi) and higher proportion of BAV compared patients without LGE. In addition, the proportion of moderate and severe AI patients was significantly higher in BAV group than in non-BAV group (P=0.009). (3) The consistency of CMR and TTE in evaluating the severity of AI patients: the agreement between TTE and CMR regarding AI severity was satisfactory (kappa value was 0.624, 95%CI 0.402-0.831, P<0.001). (4) The linear regression analysis demonstrated a negative correlation between LVEF and LGE% in BAV and non-BAV group (P<0.001). The multivariate logistic regression analysis showed that the presence of BAV was an independent risk factor of left ventricucar fibrosis (OR=5.050, 95%CI 1.220-20.908, P=0.025) after adjustment for LVEF, hypertension, LVEDVi and LVMi. Conclusion: Multi-parametric CMR provides a satisfactory noninvasive tool for estimation of myocardial fibrosis and ventricular remodeling in patients with AI, and BAV is an independent risk factor for myocardial fibrosis in patients with AI.

Percent Deviation from Midline Coaptation- When to Suspect Bicuspid Aortic Valve

Background: Bicuspid aortic valve (BAV) is typically diagnosed by visualization of aortic valve leaflet opening during systole in parasternal short axis (PSAX) echocardiographic images. The leaflets are often seen poorly in PSAX view due to suboptimal acoustic windows or poor imaging techniques but are usually seen well in parasternal long axis (PLAX) view. Although the eccentric leaflet coaptation in PLAX view has been previously described the degree of eccentricity that should alert clinicians of the presence of BAV is not established in children. The …

The Bicuspid Condition of the Aortic Valve Does Not Alter the Incidence of Accessory Coronary Artery Ostia in Syrian Hamsters (Mesocricetus auratus)

In man and Syrian hamsters (Mesocricetus auratus), the prevalence of anomalies in the origin of the coronary arteries is significantly higher in individuals with bicuspid than with normal aortic valves. In hamsters, the incidence of accessory ostia is similar in individuals with normal and anomalous coronary arteries, all of them possessing a normal (tricuspid) aortic valve. In order to evaluate whether or not the presence of bicuspid aortic valves alters the incidence of accessory ostia, 1,050 hearts from hamsters with bicuspid valves were examined. In 594 of them the coronary arteries were normal. The remaining 456 hearts showed coronary artery anomalies characterized by the absence of any artery arising from the left side of the valve. The incidence of accessory ostia was 3.9% in hamsters with normal coronary arteries and 2.2% in those with anomalous coronary patterns. Overall, 3.1% of the accessory ostia were associated with a septal artery and another 0.2% with a conal artery. These data referring to the bicuspid valves were compared with those already published on normal valves. The results of statistical analyses showed that having a bicuspid aortic valve does not alter the incidence of accessory coronary ostia. In the set of tricuspid and bicuspid valves, the incidence of accessory ostia was significantly lower on the left side than on the right side of the valve. This, together with the fact that in the present animal model the coronary anomalies were characterized by the absence of arteries on the left side of the valve, suggests that the embryonic region corresponding to the left side of the aortic valve primordium is particularly associated with preventing the normal development of coronary vessels.

Sutureless Valve Replacement Through a Right Anterior Mini-thoracotomy in Elderly Patients With Stenotic Bicuspid Aortic Valve

Several indications for sutureless aortic valve replacement (SU-AVR) have been a matter of debate. We evaluated our experience with Perceval-S (LivaNova group, Saluggia, Italy) SU-AVR in patients with severe aortic stenosis (AS) involving bicuspid aortic valve (BAV), even though presence of BAV is still considered to be a contraindication for sutureless valves. From January 2013 through March 2018, 13 patients with severe AS involving BAV underwent SU-AVR with the Perceval-S (LivaNova group, Saluggia, Italy) prosthesis in a single center. Preoperative evaluation included coronary catheterization and multisliced computerized tomography was performed in all patients. Three-dimensional transthoracic echocardiography was used to evaluate for obtaining the anatomy and phenotype of BAV. Minimally invasive approach through right anterior thoracotomy from third intercostal space was performed for all patients. The mean age was 72.8 ± 2.26 years ranging from 70 to 77, and 53.8% (n = 7) were male. The mean aortic valve gradient decreased from 46.4 ± 13.8 to 13.6 ± 4.4 mmHg postoperatively. The mean aortic valve area increased from 0.69 ± 0.22 to 1.81 ± 0.38 cm2. There was no in-hospital mortality. One patient (7.6%) had third-degree atrioventricular block requiring permanent pacemaker implantation. Mean follow-up was 15.1 ± 6.3 months (maximum 2 years). No major paravalvular leakage or valve migration occurred postoperatively. This study shows that SU-AVR is a technically feasible and safe procedure in patients with severe AS and BAV with acceptable good surgical outcomes. Presence of BAV in AS should not be considered a contraindication to Perceval-S prosthesis (LivaNova group, Saluggia, Italy).

Variants in cardiac GATA genes associated with bicuspid aortic valve.

Bicuspid aortic valve (BAV) is a heterogeneous and still not fully understood condition, with diverse genetic aetiology and associated phenotypes ranging from aortic stenosis or regurgitation to aneurysm and dissection. Several genes have been associated with the presence of BAV, notably some members of the GATA family of transcription factors that play important roles in cardiac embryogenesis. A case-control study with 122 unrelated and ethnically matched patients with bicuspid and 154 with tricuspid aortic valve was performed. All exons of GATA4, GATA5, and GATA6 genes were sequenced searching for variants. Frequencies were compared and functional effects of rare variants were analysed by informatic prediction tools. Four rare and potentially pathogenic variants were identified in only five sporadic cases: a missense p.Arg202Gln (rs782614097) in GATA5 and three synonymous variants, p.Cys274= (rs55980825) and p.His302= (rs201516339) in GATA4, and p.Asn458= (rs143026087) in GATA6. Minor alleles of p.His302=, p.Arg202Gln and rs3764962 are enriched in BAV patients compared to ExAC database (P=0.01, 0.03, and 0.01 respectively). In addition, a common polymorphism in GATA5 (p.Asp203=, rs41305803) is associated with BAV showing a protective effect in carriers of the minor allele (OR [95%CI]=0.45[0.25-0.81]; P=0.004). This study associates additional genetic variants in GATA4 and GATA5 with BAV, supporting the implication of these genes in the development of this valvulopathy. The discovery of all the genetic factors involved will contribute to a better understanding of the process and, therefore, to detect a genetic predisposition and even to the identification of therapeutic targets.

Ascending Aorta and Myocardial Mechanics in Patients with "Clinically Normal" Bicuspid Aortic Valve.

Aortic valve dysfunction and aortic wall changes are well-known complications of bicuspid aortic valve (BAV) disease. The aim of the present study was to investigate whether a remodeling process of the left ventricle (LV) is present in patients with isolated BAV. Twenty-two consecutive patients (39 ± 15 years, 9 males) with clinically normal BAV and 18 age- and gender-matched control subjects (37 ± 10 years, 9 males) were included. Cardiovascular magnetic resonance (CMR) imaging was performed to evaluate LV function, aortic valve morphology, aortic orifice area, and ascending aorta (AA) dimensions. Tissue-tracking analysis was applied to assess LV systolic and diastolic myocardial mechanics in the longitudinal, circumferential, and radial direction and AA circumferential strain (CS). No significant difference was observed between BAV and controls regarding LV ejection fraction and LV mass index. Tissue-tracking analysis demonstrated that BAV patients had significantly impaired LV systolic and diastolic myocardial mechanics. BAV patients had also significantly lower AA CS compared with controls. At multivariate analysis, the presence of BAV was the only variable significantly and independently related to the impaired AA and LV systolic myocardial mechanics. In conclusion, LV myocardial deformation properties are impaired among BAV patients. The impairment of LV systolic mechanics observed in BAV patients appears to be related only to the congenital abnormality of the aortic valve itself.

Association between flow skewness and aortic dilatation in patients with aortic stenosis.

We investigated association between hemodynamic characteristics and aortic dilatation in patients with severe aortic stenosis (AS). Eighty patients with severe AS (mean age, 67.2 ± 12.5years) who underwent multi-detector computed tomography and phase-contrast magnetic resonance imaging at the ascending aorta were retrospectively analyzed. Patients with an ascending aorta diameter >4cm had a significantly higher forward flow rate at systole (28.5 ± 6.0vs. 36.2 ± 8.6Lmin, P < 0.001), and retrograde flow rate at systole (11.3 ± 4.2vs. 18.8 ± 5.8Lmin, P < 0.001), fractional reverse ratio (a ratio of retrograde flow rate to forward flow rate; 34.1 ± 11.9% vs. 43.5 ± 18.0%, P = 0.014), flow skewness Rskewness (a ratio of sum of forward and retrograde systole flow to net systole flow rate; 2.4 ± 0.7 vs. 3.2 ± 1.0, P < 0.001). The presence of bicuspid aortic valve (BAV; odds ratio [OR] 72.01, 95% confidence interval [CI] 10.57-490.46, P < 0.001), Left ventricular mass index (LVMI; OR 1.02 /g/m2; CI 1.00-1.04, P = 0.043) and Rskewness (OR 5.6 per 1, 95% CI 1.8-17.1, P = 0.001) were associated with aortic dilatation. BAV, LVMI, and increased Rskewness in the ascending aorta are associated with aortic dilatation in patients with AS.

Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor.

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter ≥ 4.0 cm in adults, or a Z-score ≥ 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype.