Successful TAVR for a Patient with Bicuspid Aortic Valve Stenosis and Previous Type A Aortic Dissection.

Whether transfemoral transcatheter aortic valve replacement (TAVR) can be accomplished in patients with a bicuspid aortic valve (AV) and previous type A aortic dissection remains rarely addressed. We report such a case in whom transfemoral TAVR was smoothly performed employing an extraordinary long sheath to bypass the dissected aortic segment, yet at the cost of perioperative left temporoparietal infarction owing to no suitable cerebral embolic protection device available in the presence of a remaining dissection in the aortic arch. Thus, for such patients, transfemoral TAVR is still feasible but novel embolic protection devices of distinct designs should be developed to avoid perioperative cerebral embolism.

Deficient GATA6-CXCR7 signaling leads to bicuspid aortic valve.

The cardiac outflow tract (OFT) transiently links the ventricles to the aortic sac and forms the arterial valves. Abnormalities in these valves, such as bicuspid aortic valve (BAV), are common congenital anomalies. GATA6-inactivating variants cause cardiac OFT defects and BAV, but their mechanisms are unclear. We generated Gata6STOP/+ mice using CRISPR-Cas9, which show highly penetrant BAV (70%) and membranous ventricular septal defects (43%). These mice exhibited decreased proliferation and increased ISL1-positive progenitor cells in the OFT, indicating abnormal cardiovascular differentiation. Gata6 deletion with the Mef2cCre driver line recapitulated Gata6STOP/+ phenotypes, indicating a cell-autonomous role for Gata6 in the second heart field. Gata6STOP/+ mice showed reduced OFT length and caliber, associated with deficient cardiac neural crest cell contribution, which may cause valvulo-septal defects. RNA-sequencing analysis showed depletion in pathways related to cell proliferation and migration, highlighting Cxcr7 (also known as Ackr3) as a candidate gene. Reduced mesenchymal cell migration and invasion were observed in Gata6STOP/+ OFT tissue. CXCR7 agonists reduced mesenchymal cell migration and increased invasion in wild-type but not in Gata6STOP/+ explants, indicating the GATA6-dependent role of CXCR7 in OFT development and its potential link to BAV.

Impact of Balloon-Expandable TAVR Valve Deformation and Calcium Distribution on Outcomes in Bicuspid Aortic Valve.

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).

Rare genomic copy number variants implicate new candidate genes for bicuspid aortic valve.

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in a BAV cohort with late onset sporadic disease (n = 5040). We identified 3 large and rare (< 1,1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 9% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.

A Case Report of Modified Cabrol Technique in a 60-Year-Old Male with Coronary Origin Anatomical Variant.

Introduction: Reconstruction surgery of the proximal aorta in most cases involves the use of an aortic conduit, followed by reimplantation of the coronary ostia. Although uncommon, the origin of the coronary arteries in certain anatomical variants poses additional difficulties when performing surgery on the aortic root and requires a different treatment rationale. Case report: We hereby present the case of a 60-year-old patient with multiple cardiovascular risk factors (smoking, arterial hypertension and dyslipidemia), suffering from severe degenerative stenosis of a bicuspid aortic valve, associated with ascending aorta aneurysm and a significant extrinsic stenosis of the left coronary artery caused by the aneurysm. The patient presented with severe degenerative bicuspid aortic valve stenosis associated with ascending aorta aneurysm and a significant extrinsic stenosis of the left coronary artery caused by the aneurysm. Following the preoperative assessment, it was decided that the best course of action was to perform surgery on the aortic valve and ascending aorta. During the surgery, the origin of the right and left coronary ostia were found at the level of the left coronary cusp, both forming a common coronary button. Due to this particular anatomical variant, it was decided to reimplant them as a common button onto the main conduit by means of an interposed No.10 PTFE (Polytetrafluoroethylene) vascular prosthesis. Conclusion: A rare case of aortic root surgery associated with coronary ostia origin variant "shotgun barrel", which required a different method of reimplantation: modified Cabrol technique.

"One-stop" interventional therapy for quadricuspid aortic valve combined with severe coronary artery disease: a case report.

Congenital Quadricuspid Aortic Valve (QAV) malformation is a relatively rare cardiac valve malformation, especially with abnormal coronary opening and severe stenosis of Coronary Artery Disease (CAD). The patient underwent "one-stop" interventional treatment with transcatheter aortic valve replacement and percutaneous coronary stent implantation. Follow up for 12-month with good outcomes.

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

BACKGROUND: The 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. METHODS: We 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 CONCLUSIONS: Among 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.

Infective Endocarditis in Patients With Bicuspid Aortic Valves: Unique Clinical and Microbiologic Features.

OBJECTIVE: Patients with bicuspid aortic valves (BAV) are at increased risk of infective endocarditis (IE). Information of the clinical presentation and the microbiology of BAV-associated IE, however, is limited. Therefore, our study aimed to characterise the clinical features native valve endocarditis (NVE) in the setting of BAV and compared them to patients with prosthetic valve endocarditis (PVE) following BAV replacement. METHODS: Adult patients with BAV or history of BAV with aortic valve replacement (AVR) and a definite or possible IE diagnosis within the Mayo Clinic Enterprise (USA) from January 2008 to December 2021, were included. BAV was confirmed by trans-oesophageal echocardiography. IE was defined according to the modified Duke criteria and only an initial episode was included. Statistical analyses were performed to compare clinical characteristics, microbiology, and IE complications. RESULTS: Overall, 161 patients with BAV and IE (NVE [n=60], 37.3%) and PVE [n=101, 62.7%) were included. Mean age±SD was 56.5±16.1 years, and 139 (86.3%) patients were males. PVE patients were older (p<0.01) and had a higher rate of hypertension (p<0.01), chronic heart failure (p<0.01), chronic kidney disease (p<0.01), and perivalvular abscess (p<0.01). BAV patients with NVE had a higher prevalence of isolated mitral valve IE (p<0.01), moderate to severe aortic valve regurgitation (p<0.01) and combined aortic with mitral valve IE (p<0.01). Streptococcus mitis was the most common pathogen in NVE (30.0%) while Staphylococcus aureus was the most common in PVE (15.8%). CONCLUSIONS: Patients with BAV are at risk of both NVE and PVE. Each syndrome has unique clinical features, including microbiologic findings, that should be appreciated in IE diagnosis and management.

Calcific Aortic Stenosis - Inflammatory Disease.

In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease and cause for valve replacement. The prevalence of the disease increases with age, reaching over 5 % in adults over 75 years of age. The cases of CAS are classified as either of a previously normal (tricuspid) aortic valve (senile, syn. age - related, "sclerotic" type), or based on a congenitally malformed, usually bicuspid aortic valve. This paper is a brief summary of our 5 previous publications from the years 2007 - 2021, devoted to histopathology of CAS, namely to vascularization, inflammatory infiltrate and metaplastic ossification of the valve, and also to topography of these lesions in individual valve cusps. We conclude that calcification of the aortic valve is not a passive degenerative lesion, but an active multifactorial inflammatory process driven by cells native to the aortic valve. Pathogenesis of CAS is similar to that of atherosclerosis.

Prognostic value of the electrocardiogram in patients with bicuspid aortic valve disease.

BACKGROUND: Identifying bicuspid aortic valve (BAV) patients at risk for cardiac events remains challenging and the role of the electrocardiogram (ECG) has not yet been described. Therefore, this study aims to describe ECG parameters in BAV patients, and investigate their prognostic value. METHODS: In this single-center prospective study patients with BAV without a prior aortic valve replacement (AVR) were included. Transthoracic echocardiogram and 12­lead resting-ECG were obtained. Associations between ECG parameters and the composite endpoint of all-cause mortality and AVR were assessed using Cox-proportional hazard analysis. RESULTS: 120 patients with BAV were included (median age 30 years, 61% male). Median aortic jet velocity was 2.4 m/s [IQR: 1.7-3.4] and 5 patients (4%) had severe aortic regurgitation. All patients were in sinus rhythm. Any ECG abnormality was present in 57 patients (48%). Median PR-interval was 156 [IQR: 138-170] msec. A deviating QRS axis was found in 17 patients (14%) and Cornell criteria for LVH were fulfilled in 20 patients (17%). Repolarization abnormalities were present in 12 patients (10%). Median follow-up duration was 7.0 [6.3-9.8] years, during which 23 patients underwent AVR and 2 patients died. After adjusting for age, a longer PR-interval was associated with worse intervention-free survival (HR 1.02, 95% CI: 1.01-1.04). CONCLUSION: Almost half of the patients with BAV had abnormalities on their ECG. Moreover, the PR-interval may be an interesting prognostic marker for intervention-free survival in BAV patients.

Comprehensive imaging evaluation of the aortic valve and root before aortic root surgery: a study comparing MDCT and TEE.

OBJECTIVE: To investigate the accuracy and consistency of MDCT and TEE in the preoperative assessment of aortic root surgery. METHODS: From January 2021 to September 2022, 118 patients who underwent aortic root surgery were included in this study. All patients underwent high-quality preoperative MDCT and TEE examinations, and the examination results were independently measured and assessed by two senior radiologists or ultrasound specialists. Bland-Altman analysis and Pearson correlation testing were employed to assess the correlation and consistency between MDCT and TEE. These analyses were then compared with actual intraoperative measurement data. RESULTS: Among all the patients, 73 (61.86%) had tricuspid aortic valve (TAV), and 45 (38.14%) had bicuspid aortic valve (BAV). A comparison between the TEE and MDCT measurements showed that for the annulus diameter, the area-derived diameter had the best correlation and agreement. For the sinus of Valsalva diameter, the circumference-derived diameter was optimal. However, for the STJ diameter, the minimum cross-sectional diameter showed the best agreement with TEE. In contrast, measurements of geometric height showed a weaker correlation and agreement. CONCLUSION: Contrast-enhanced MDCT can be a valuable tool for perioperative evaluation in aortic root surgery, with good correlation, consistency, and feasibility when compared to TEE. The choice of MDCT measurement methodology, specifically area-derived and circumference-derived diameter, proved to be more accurate than other methods. Further research is required to enhance the understanding of aortic valve repair and associated imaging techniques.

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

OBJECTIVES: The aims of the present study were to compare the long-term outcomes for ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve ( TAV). METHODS: This retrospective study included 310 patients who had undergone isolated aortic valve replacement with an ascending aorta diameter ≤ 45 mm between January 2010 and September 2021. The patients were divided into BAV group (n=90) and TAV group (n=220). The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed. RESULTS: Overall survival was 89 ± 4% in the BAV group vs. 75 ± 6% in the TAV group at 10 years postoperatively (P=0.007), yet this difference disappeared after adjusting exclusively for age (P=0.343). The mean annual growth rate of the ascending aorta was similar between the two groups during follow-up (0.5 ± 0.6 mm/year vs. 0.4 ± 0.5 mm/year; P=0.498). Ten-year freedom from adverse aortic events was 98.1% in the BAV group vs. 95.0% in the TAV group (P=0.636). Multivariable analysis revealed preoperative ascending aorta diameter to be a significant predictor of adverse aortic events (hazard ratio: 1.76; 95% confidence interval: 1.33 to 2.38; P<0.001). CONCLUSION: 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.

3-Year Outcomes From the Evolut Low Risk TAVR Bicuspid Study.

BACKGROUND: Outcomes from transcatheter aortic valve replacement (TAVR) in low-surgical risk patients with bicuspid aortic stenosis beyond 2 years are limited. OBJECTIVES: This study aimed to evaluate 3-year clinical and echocardiographic outcomes from the Evolut Low Risk Bicuspid Study. METHODS: The Evolut Low Risk Bicuspid Study is a prospective, multicenter, single-arm study conducted in 25 U.S. CENTERS: Patients with severe aortic stenosis at low surgical risk with bicuspid aortic valve anatomy (all subtypes) underwent TAVR with a self-expanding, supra-annular Evolut R or PRO (Medtronic) bioprosthesis. An independent clinical events committee adjudicated all deaths and endpoint-related adverse events, and a central echocardiographic core laboratory assessed hemodynamic endpoints. RESULTS: An attempted implant was performed in 150 patients from December 2018 to October 2019. The mean age was 70.3 ± 5.5 years, 48% (72/150) of the patients were women, and the mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 1.3% (Q1-Q3: 0.9%-1.7%). Sievers type 1 was the dominant bicuspid morphology (90.7%, 136/150). The Kaplan-Meier rates of all-cause mortality or disabling stroke were 1.3% (95% CI: 0.3%-5.3%) at 1 year, 3.4% (95% CI: 1.4%-8.1%) at 2 years, and 4.1% (95% CI: 1.6%-10.7%) at 3 years. The incidence of new permanent pacemaker implantation was 19.4% (95% CI: 12.4%-29.6%) at 3 years. There were no instances of moderate or severe paravalvular aortic regurgitation at 2 and 3 years after TAVR. CONCLUSIONS: The 3-year results from the Evolut Low Risk Bicuspid Study demonstrate low rates of all-cause mortality or disabling stroke and favorable hemodynamic performance.

Smooth muscle cell phenotypic switching occurs independent of aortic dilation in bicuspid aortic valve-associated ascending aortas.

BACKGROUND: Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow perturbations, are likely involved. Since loss of contractility and elaboration of extracellular matrix in the vessel wall are features of BAV-associated aortopathy, phenotypic modulation of smooth muscle cells (SMCs) may play a role. METHODS: Ascending aortic tissue was collected intra-operatively from 25 individuals with normal (i.e., tricuspid) aortic valves (TAV) and from 25 individuals with BAVs. For both TAV and BAV, 10 patients had non-dilated (ND) and 15 patients had dilated (D) aortas. SMCs were isolated and cultured from a subset of patients from each group. Aortic tissue and SMCs were fluorescently immunolabeled for SMC phenotypic markers (i.e., alpha-smooth muscle actin (ASMA, contractile), vimentin (synthetic) and p16INK4a and p21Cip1 (senescence). SMCs were also analyzed for replicative senescence in culture. RESULTS: In normal-sized and dilated BAV aortas, SMCs switched from the contractile state to either synthetic or senescent phenotypes, as observed by loss of ASMA (ND: P = 0.001, D: P = 0.002) and associated increases in vimentin (ND: P = 0.03, D: P = 0.004) or p16/p21 (ND: P = 0.03, D: P<0.0001) compared to TAV. Dilatation of the aorta exacerbated SMC phenotypic switching in both BAV and TAV aortas (all P<0.05). In SMCs cultured from normal and dilated aortas, those isolated from BAV reached replicative senescence faster than those from TAV aortas (all P = 0.02). Furthermore, there was a stark inverse correlation between ASMA and cell passage number in BAV SMCs (ND: P = 0.0006, D: P = 0.01), but not in TAV SMCs (ND: P = 0.93, D: P = 0.20). CONCLUSIONS: The findings of this study provide direct evidence from cell culture studies implying that SMCs switch from the contractile state to either synthetic or senescent phenotypes in the non-dilated BAV aorta. In cultured SMCs from both non-dilated and dilated aortas, we found that this process may precede dilatation and accompany aneurysm development in BAV. Our findings suggest that therapeutically targeting SMC phenotypic modulation in BAV patients may be a viable option to prevent or delay ascending aortic aneurysm formation.

A 25-Year-Old With an Incidentally Detected Ascending Thoracic Aortic Aneurysm and Bicuspid Aortic Valve.

A woman had shortness of breath and a first-degree relative with a history of ascending aorta dissection. Imaging showed an isolated dilatation in the mid ascending aorta and a bicuspid aortic valve but no pulmonary infiltrates, effusion, or embolism and no aortic stenosis or regurgitation. What would you do next?