Bicuspid Aortic Valve Insufficiency Research Articles

Variable clinical expression of a Belgian TGFB3 founder variant suggests the presence of a genetic modifier.

Background: TGFB3 variants cause Loeys-Dietz syndrome type 5, a syndromic form of thoracic aortic aneurysm and dissection. The exact disease phenotype is hard to delineate because of few identified cases and highly variable clinical representation. Methodology: We provide the results of a haplotype analysis and a medical record review of clinical features of 27 individuals from 5 different families, originating from the Campine region in Flanders, carrying the NM_003239.5(TGFB3):c.787G>C p.(Asp263His) likely pathogenic variant, dbSNP:rs796051886, ClinVar:203492. The Asp263 residue is essential for integrin binding to the Arg-Gly-Asp (RGD) motif of the TGFβ3-cytokine. Results: The haplotype analysis revealed a shared haplotype of minimum 1.92Mb and maximum 4.14Mb, suggesting a common founder originating >400years ago. Variable clinical features included connective tissue manifestations, non-aneurysmal cardiovascular problems such as hypertrophic cardiomyopathy, bicuspid aortic valve, mitral valve disease, and septal defects. Remarkably, only in 4 out of the 27 variant-harboring individuals, significant aortic involvement was observed. In one family, a 31-year-old male presented with type A dissection. In another family, the male proband (65years) underwent a Bentall procedure because of bicuspid aortic valve insufficiency combined with sinus of Valsalva of 50mm, while an 80-year-old male relative had an aortic diameter of 43mm. In a third family, the father of the proband (75years) presented with ascending aortic aneurysm (44mm). Conclusion: The low penetrance (15%) of aortic aneurysm/dissection suggests that haploinsufficiency alone by the TGFB3 variant may not result in aneurysm development but that additional factors are required to provoke the aneurysm phenotype.

The possibilities of valve-sparing surgical treatment of bicuspid aortic valve syndrome

The Bentall procedure is the gold standard for the treatment of bicuspid aortic valve insufficiency, aortic root aneurysm and ascending aortic aneurysm today. Valve-sparing methods of reconstruction of the aortic root are becoming increasingly common, with the accumulation of experience in the reconstruction of the bicuspid aortic valve and more favorable hemodynamic characteristics of the native valve compared to any prosthesis. The purpose of our study is to determine the indications for surgical correction of BAV-related aortopathy and the most effective method of surgical treatment. We performed a literature review of the variants of valve-sparing surgical treatment of bicuspid aortic valve syndrome, which have shown satisfactory med-term and long-term results. The article will be interested to cardiovascular surgeons and cardiologists.Received 6 December 2021. Revised 15 February 2022. Accepted 5 March 2022.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Contribution of the authors: The authors contributed equally to this article.

Repair of insufficient aortic valve and single coronary artery with intramural course.

We report about a patient with severe bicuspid aortic valve insufficiency and a single coronary artery with an intramural course. Aortic valve repair with double plication and coronary translocation was satisfactory.

Bicuspid aortic valve repair with external or subcommissural annuloplasty-echocardiographic prospective trial.

The incompetent bicuspid aortic valve (BAV) can be repaired using various techniques. This study presents a prospective comparison of external and subcommissural aortic annuloplasty. Fifty consecutive patients (38 males, age: 43.9 ± 15.8 years) with BAV insufficiency with or without aortic dilatation underwent valve repair in a single institution. They were prospectively allocated to one of two groups based on the aortic annulus stabilization technique: 25 patients were operated on using the subcommissural annuloplasty (SCA) and 25 using the external complete annuloplasty (EA). Transthoracic echocardiography was performed in all patients before the operation and 1 and 3 years after the operation. Moreover, mortality and morbidity at 7 years were evaluated. In prospective echocardiographic comparison, EA was associated with smaller diameter of the aortic annulus (24.1 ± 2.6 mm vs. 25.8±2.1 mm, p < .05) and lower mean and peak transvalvular gradients (7 ± 4 mmHg vs. 13 ± 4 mmHg, p = .02 and 15.3 ± 9.7 mmHg vs. 20.7 ± 5.6 mmHg, p = .03, respectively). No patients died or required reoperation due to recurrent insufficiency at 6,81 (interquartile range-0,17) years after the operation. The Kaplan-Meier actuarial freedom from aortic regurgitation(AR) grade =2 or gradient > 20 mmHg at 35.1 ± 3.6 months years was 96% (24 out of 25) for patients who had external annuloplasty and amounted to 76% (19 out of 25) for those who had SCA, p = .05). External annuloplasty performed during repair of the BAV is associated with better hemodynamics at medium-term follow-up compared to SCA.

External or subcomissural annuloplasty in bicuspid aortic valve repair: Which is better?

Patients with a bicuspid aortic valve (BAV) are at increased risk of valvular regurgitation compared to their counterparts with a tri-leaflet aortic valve. There is now increasing emphasis to offer BAV repair to mitigate the risks of prosthesis-related complications, including thromboembolism, hemorrhage and endocarditis, as well as structural valve deterioration and future reoperation with conventional valve replacement, particularly in younger populations. Furthermore, over the preceding two decades, our greater understanding of the functional anatomy of the BAV, pathophysiological mechanisms of BAV insufficiency, and the development of a functional classification of aortic regurgitation have significantly contributed to the evolution of aortic valve reconstructive surgery. In this commentary, we discuss a recent article from the Journal of Cardiac Surgery comparing external annuloplasty and subcommissural annuloplasty as techniques for BAV repair.

Bicuspid aortic valve repair: outcomes after 17 years of experience.

OBJECTIVESThis study presents the results of 17 years of experience with bicuspid aortic valve (BAV) repair and the analysis of factors associated with repair failure and early echocardiographic outcome. METHODSBetween 2003 and 2020, a total of 206 patients [mean age: 44.5 ± 15.2 years; 152 males (74%)] with BAV insufficiency with or without aortic dilatation underwent elective aortic valve repair performed by a single surgeon with a mean follow-up of 5 ± 3.5 years. The transthoracic echocardiography examinations were reported.RESULTSThere were no deaths during the hospital stay, and all but 1 patient survived the follow-up period (99.5%). Overall, 10 patients (5%) developed severe insufficiency and 2 (1%) developed aortic dilatation requiring reoperation. Freedom from reoperation at 7 years reached 91.8%. Type 2 BAV configuration [hazard ratio (HR) 3.9; 95% confidence interval (CI): 1.01–60; P = 0.049], no sinotubular junction remodelling (HR 7; 95% CI: 1.7–23; P = 0.005), no circumferential annuloplasty (HR 3.9; 95% CI: 1.01–64; P = 0.047) and leaflet resection (HR 5.7; 95% CI 1.2–13. P = 0.017) have been identified as a risk factor of redo operation. Parameters of the postoperative left ventricle reverse remodelling improved significantly early after the operation and later at 2 years evaluation.CONCLUSIONSThe repair of BAV offers good short- and mid-term results providing a significant reverse left ventricular remodelling. Type 0 BAV preoperative configuration, circumferential annuloplasty and sinotubular junction remodelling are associated with better repair durability.

Repair of Bicuspid Aortic Valve Insufficiency with Associated Ascending Aortic Aneurysm Using Geometric Ring Annuloplasty

Repair of Bicuspid Aortic Valve Insufficiency with Associated Ascending Aortic Aneurysm Using Geometric Ring Annuloplasty

Factors impacting long-term pulmonary autograft durability after the Ross procedure

ObjectiveAlthough the Ross procedure provides excellent long-term survival and a high quality of life, its use has been limited to relatively few centers. In this study, we evaluated long-term Ross procedure results in adults to assess the predictors of pulmonary autograft durability. MethodsBetween 1998 and 2015, 793 consecutive adult patients underwent the Ross procedure. The total root replacement technique was used in all patients. ResultsThe early mortality rate was 2.9%. The mean follow-up duration was 6.5 ± 3.2 years, and the 10-year survival rate was 90.4%. Longitudinal mixed-effects ordinal regression identified a combination of bicuspid aortic valve and aortic insufficiency (odds ratio, 2.19; P < .001) as predictors for progression of autograft valve insufficiency at follow-up. The cumulative incidence of autograft reoperations at 10 years was 8.6%. Competing risk regression identified bicuspid aortic valve insufficiency as the independent predictor of autograft reoperation (subdistribution hazard ratio, 2.16; P = .030). Moreover, patients with bicuspid aortic valve and aortic insufficiency had greater increases in annulus (P < .001), sinus (P < .001), and ascending aorta (P < .001) diameters over time. ConclusionsFor patients undergoing the Ross procedure, a combination of bicuspid aortic valves and aortic insufficiency is the main risk factor for late autograft dilatation and dysfunction.

Morphologic and Functional Markers of Aortopathy in Patients With Bicuspid Aortic Valve Insufficiency Versus Stenosis

Bicuspid aortic valve (BAV)-associated aortopathy is heterogeneous and still insufficiently defined. We prospectively analyzed the morphologic and functional variables of aortopathy in patients undergoing operations for BAV insufficiency (BAV-AI) vs stenosis (BAV-AS). A total of 172 consecutive patients (71% male, 59 ± 10 years) underwent aortic valve replacement with orwithout proximal aortic operation for BAV-AS (n=137), and BAV-AI (n= 35) from January 2012 through December 2014. All patients underwent preoperative cardiac magnetic resonance imaging to evaluate morphologic and functional variables of the aortic root. Magnetic resonance imaging data were used to guide sampling of aortic tissue intraoperatively (ie, from the area where flow jet impacts on the aortic wall [jet sample] and the opposite aortic wall [control sample]). Aortic wall lesions were graded based on the histologic sum score (range, 0 to 21). Expression and severity of aortopathy were quantified by means of proximal aortic phenotype, indexed aortic diameters, and a sum score. Cross-sectional aortic diameters were significantly larger in the BAV-AI group vs the BAV-AS group (47 ± 8 mm vs 41 ± 8 mm, p= 0.001). Moreover, root dilatation phenotype was more frequent in the BAV-AI group (27% vs 6%, p= 0.01) and was associated with a significantly larger aortic annulus diameter (32 ± 3 mm vs 27 ± 3 mm, p < 0.001). The histologic sum score was significantly different between the study groups (3.7 ± 2.6 BAV-AI vs 2.5 ± 1.4 BAV-AS, p= 0.03). Logistic regression revealed a significant association between BAV-AI and indexed aortic diameter exceeding 22 mm/m2 (odds ratio, 4.7; p= 0.007). Our study demonstrates that BAV functional phenotype correlates significantly with the expression and severity of bicuspid aortopathy.

Invited Commentary

In this issue of The Annals, Wang and colleagues [1Wang Y. Wu B. Li J. Dong L. Wang C. Shu X. Impact of aortic insufficiency on ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement in patients with a bicuspid aortic valve.Ann Thorac Surg. 2016; 101: 1707-1715Abstract Full Text Full Text PDF Scopus (36) Google Scholar] reported follow-up data of a large cohort of consecutively treated patients who underwent isolated aortic valve replacement (AVR) surgery for bicuspid aortic valve (BAV) disease. The authors should be congratulated for their efforts to determine the fate of proximal aortopathy in BAV patients stratified on the pattern of aortic valve dysfunction, namely, BAV–aortic stenosis versus BAV–aortic insufficiency (AI). Indeed, there is an emerging evidence of the coexistence of distinct clinical entities of BAV disease, namely, those presenting with predominant aortic valve stenosis (ie, BAV stenosis phenotype) and those presenting with predominant aortic insufficiency and dilation of the aortic root (ie, BAV root phenotype). Given the evident paucity of homogeneous phenotype-specific reporting of outcomes in BAV disease, the current report [1Wang Y. Wu B. Li J. Dong L. Wang C. Shu X. Impact of aortic insufficiency on ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement in patients with a bicuspid aortic valve.Ann Thorac Surg. 2016; 101: 1707-1715Abstract Full Text Full Text PDF Scopus (36) Google Scholar] is of great clinical value and should be a good example for future BAV studies. The major focus of this paper is on a cohort of BAV patients presenting with aortic valve insufficiency and aortic root involvement (ie, root phenotype). Wang and colleagues [1Wang Y. Wu B. Li J. Dong L. Wang C. Shu X. Impact of aortic insufficiency on ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement in patients with a bicuspid aortic valve.Ann Thorac Surg. 2016; 101: 1707-1715Abstract Full Text Full Text PDF Scopus (36) Google Scholar] found a significantly increased ascending aortic growth rate and higher prevalence of aortic events in BAV-AI patients, which is in line with our previous data [2Girdauskas E. Disha K. Rouman M. Espinoza A. Borger M.A. Kuntze T. Aortic events after isolated aortic valve replacement for bicuspid aortic valve root phenotype: echocardiographic follow-up study.Eur J Cardiothorac Surg. 2015; 48: e71-e76Crossref PubMed Scopus (41) Google Scholar, 3Girdauskas E. Rouman M. Disha K. et al.Aortic dissection after previous aortic valve replacement for bicuspid aortic valve disease.J Am Coll Cardiol. 2015; 66: 1409-1411Crossref PubMed Scopus (47) Google Scholar] and therefore indicate the genetic origin of BAV-AI associated aortopathy. In retrospect, these data show convincingly that the historically reported increased risk of aortic events in BAV disease is mainly due to the mixing of such root phenotype patients in the analyzed heterogeneous BAV cohorts. The congenital nature of aortopathy in root phenotype patients is further supported by common phenotypic features (ie, young male BAV patients) and involvement of adjacent cardiac structures—marked enlargement of aortoventricular junction, involvement of anterior mitral leaflet (ie, WAMBIRE complex [4Sievers H.H. Invited commentary.Ann Thorac Surg. 2009; 87: 82Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar]), defects/aneurysms of membranous interventricular septum, and coexistent coronary anomalies. Similar to other well-known connective tissue disorders, several noncardiac manifestations (eg, skeletal deformities, recurrent groin hernia, and cerebral arterial aneurysms) have been previously reported in BAV insufficiency cohorts. Prospective trials aiming to clarify the underlying gene expression and biomarker patterns in BAV root phenotype patients are under way, and their results are awaited eagerly. The proof of congenital background of BAV-AI associated aortopathy will undoubtedly change our current understanding of BAV disease complex and make this distinct entity to become a firm part in the novel BAV nomenclature. Impact of Aortic Insufficiency on Ascending Aortic Dilatation and Adverse Aortic Events After Isolated Aortic Valve Replacement in Patients With a Bicuspid Aortic ValveThe Annals of Thoracic SurgeryVol. 101Issue 5PreviewAberrant flow pattern and congenital fragility bestows bicuspid aortic valve (BAV) with a propensity toward ascending aorta dilatation, aneurysm, and dissection. Whether isolated aortic valve replacement (AVR) can prevent further dilatation in BAV ascending aorta and what indicates concurrent aortic intervention in the case of valve operation remain controversial. Full-Text PDF

Mitral regurgitation after previous aortic valve surgery for bicuspid aortic valve insufficiency.

Regurgitant bicuspid aortic valves (BAV) are reported to be associated with myxomatous degeneration of the anterior mitral leaflet. We examined the risk of late new-onset mitral regurgitation (MR) in patients who underwent aortic valve/aortic root surgery for BAV regurgitation and concomitant root dilatation. A total of 97 consecutive patients (47±11 years, 94% men) were identified from our institutional BAV database (N.=640) based on the following criteria: 1) BAV regurgitation; 2) aortic root diameter >40 mm; 3) no relevant mitral valve disease (i.e., MR<2+) and no simultaneous mitral intervention at the time of BAV surgery. All patients underwent isolated aortic valve replacement (AVR subgroup, N.=59) or aortic root replacement with a composite graft (i.e., for root aneurysm >50 mm) (ARR subgroup, N.=38) from 1995 through 2008. Echocardiographic follow-up (1009 patient-years) was obtained for all 96 (100%) hospital survivors. The primary endpoint was freedom from new-onset MR>2+ and redo mitral valve surgery. Nine patients (9.4%) showed new-onset MR>2+ after mean echocardiographic follow-up of 10.4±4.0 years postoperatively. Myxomatous degeneration and prolapse of the anterior mitral leaflet was found in all 9 patients, and the posterior leaflet was involved in 3 of them. Two patients (2%) in AVR subgroup underwent re-do mitral surgery. No MR>2+ occurred in ARR subgroup. Freedom from MR>2+ or mitral surgery at 15 years was significantly lower in AVR subgroup vs. ARR subgroup (i.e., 38% vs. 100%, P=0.01). The risk of new-onset MR is significantly increased in patients with BAV regurgitation and aortic root dilatation who undergo isolated AVR rather than root replacement. The mechanism by which aortic root replacement may prevent the occurrence of late MR in BAV root phenotype patients is to be determined.

Aortic events after isolated aortic valve replacement for bicuspid aortic valve root phenotype: echocardiographic follow-up study.

Various forms of bicuspid aortic valve (BAV) aortopathy exist, and the optimal treatment for the different subgroups is insufficiently defined. We aimed to analyse the risk of adverse aortic events after aortic valve replacement (AVR) for BAV insufficiency and concomitant mild-to-moderate dilatation of the aortic root (i.e. BAV root phenotype). A total of 56 consecutive patients (mean age 47 ± 11 years, 95% men) with BAV insufficiency and a root diameter of 40-50 mm underwent AVR surgery from 1995 to 2008. All patients, as identified from our institutional BAV database, had a dilated aortic annulus (i.e. defined as valve prosthesis size ≥27 mm) without aortic stenosis (i.e. mean gradient ≤20 mmHg). Patients who underwent concomitant aortic surgery were excluded. Follow-up (622 patient-years) including echocardiography data was available for all patients. Aortic events were defined as the need for proximal aortic surgery, the occurrence of aortic dissection/rupture, echocardiographic evidence of increasing aortic root diameter/occurrence of late paravalvular leakage or sudden death during follow-up. Actuarial survival was 90% at 10 years and 78% at 15 years. Adverse aortic events occurred in 19 (34%) study patients. Redo aortic surgery was performed in 6 patients (11%), 2 of which were for aortic dissection. Four patients (7%) suffered sudden cardiac death. Moreover, follow-up echocardiography revealed a significant, progressive enlargement of the aortic root diameter in 7 (13%) patients and occurrence of late de novo paravalvular leakage in 2 (3%) patients. The resultant freedom from aortic events was 81% at 10 years and 51% at 15 years. Patients with a BAV root phenotype are at significant risk of aortic events after isolated AVR. Simultaneous root/ascending aortic surgery should be strongly considered in such patients.

Aortic root geometry in bicuspid aortic insufficiency versus stenosis: implications for valve repair.

The contribution of aortic annular and root disease in bicuspid aortic valve (BAV) insufficiency remains unclear. We compared aortic root geometry between BAV stenosis and aortic insufficiency (AI), before and after repair. Patients presenting for surgery for BAV insufficiency (n = 58) were compared with patients with BAV stenosis (n = 58). Clinical and transoesophageal echocardiographic data were collected, including end-diastolic diameters of the ventriculo-aortic junction (VAJ), aortic root, sinotubular junction (STJ) and ascending aorta (AA). AI patients were younger and more likely to be male compared with aortic stenosis (AS) patients. VAJ, aortic root and STJ diameters were significantly larger in AI compared with AS patients (30 ± 0.5 vs 25 ± 0.4 mm, P < 0.001; 41 ± 0.8 vs 34 ± 0.6 mm, P < 0.001; 36 ± 0.9 vs 30 ± 0.6 mm, P < 0.001, respectively). Following multivariable adjustment for age, sex, body surface area and ascending aortic diameter, these diameters remained larger in AI patients with a mean difference of 3, 6 and 4 mm, respectively (all P < 0.001). Mean AA diameter in the AI group was similar to the AS group (37 ± 1.0 vs 34 ± 0.8 mm, P = 0.06). Forty (69%) AI patients had BAV repair with a mean reduction in VAJ and STJ diameters of 5 and 9 mm compared with prerepair (P < 0.0001). Despite the absence of aortic aneurysms, aortic annulus and root dimensions are significantly larger in patients with BAV insufficiency compared with stenosis. Alterations in aortic root geometry contribute to the pathophysiology of BAV insufficiency and require correction for a successful repair.

Is there any difference in aortic wall quality between patients with bicuspid aortic valve stenosis and those with bicuspid aortic valve insufficiency?

We read with a great interest the manuscript by Benedik et al. [1] published in the recent issue of European Journal of CardioThoracic Surgery. Benedik et al. should be congratulated for prospectively addressing the issue of proximal aortic disease in aortic valve stenosis vs aortic valve insufficiency in a reasonable number of consecutively enrolled patients. The background of this study is of great interest and absolutely well-taken, as patients with aortic valve insufficiency have been repeatedly demonstrated to be at higher risk of late aortic events after isolated aortic valve replacement (AVR) surgery [2]. The findings of this study are in line with the previous reports and support once again common surgical observation that, in terms of aortopathy, aortic valve insufficiency is a different clinical entity when compared with valve stenosis. However, we would like to focus our comment on the bicuspid aortic valve (BAV) entity. The authors addressed this issue in their previous manuscript [3] and were unable to find any difference in the aortic wall cohesion between patients with tricuspid aortic valve (TAV) and those with BAV disease. Results from their previous study [3] may explain the fact that the authors did not split their study population into TAV and BAV cohorts in their current series [1]. However, aortic valve stenosis was the predominant valve pathology in the majority of patients in both (i.e. TAV and BAV) cohorts in their comparative analysis [3] and barely 9 (5%) patients with BAV insufficiency were included. Our recent data strongly suggest that aortopathy in BAV stenosis is predominantly of haemodynamic origin and has a comparable clinical course as an aortopathy in TAV stenosis [4]. However, BAV is a heterogeneous disorder [5] and patients with an isolated BAV insufficiency (so-called root phenotype) may have a completely distinct form of aortopathy that may follow a different clinical course after AVR surgery [6]. Therefore, the results from comparative analysis of aortopathy between patients with BAV and those with TAV stenosis may not be generalizable to the whole BAV population. As the recent study [1] includes a reasonable number of patients with aortic valve insufficiency and a significant proportion of them are presumably bicuspid (i.e. share the typical features of root phenotype), differential analysis of BAV and TAV aortopathy in the stenosis and insufficiency subgroups would be very welcoming. Potentially, this supplemental analysis would be a nice contribution to the controversial area of BAV-associated aortopathy.

Risk of proximal aortic dissection in patients with bicuspid aortic valve: how to address this controversy?

The risk of acute aortic events in patients with bicuspid aortic valve (BAV) disease is a controversial issue. The real risk of aortic dissection in patients with BAV disease is unknown. An indirect assessment of this risk, however, could be gained with a more detailed understanding of the pathogenesis of BAV aortopathy. There are two major issues that should be clarified before one addresses the question of aortic dissection risk in BAV patients. The first issue, when analysing the data from previous BAV cohorts, is to determine what stage of BAV disease was present in the described patient population. In particular, was the risk of aortic dissection in BAV patients determined before or after aortic valve replacement (AVR) surgery? The second issue to consider is the functional state of the pathological valve within the observed population. In particular, did patients predominantly suffer from BAV stenosis or BAV insufficiency? Unfortunately, the vast majority of published reports do not separate between the different BAV phenotypes, thereby complicating interpretation of the results. Considering these two important clinical variables (i.e. the stage of BAV disease and the functional phenotype), we herein aim to explain the inconsistency of the published data with regard to the risk of aortic dissection in patients with BAV disease.

EComment. Evaluating aortic media changes in ascending aorta aneurysm with bicuspid aortic valve disease

We read with great interest the paper by Girdauskas and colleagues who found that patients with bicuspid aortic valve (BAV) insufficiency and a proximal aorta of ≥50 mm had a significantly higher rate of moderate/severe proximal aortic media elastic fibre loss as compared to their counterparts with BAV stenosis [1]. We would like to add some thoughts about other fields of investigation between patients with BAV stenosis versus BAV insufficiency and ascending aorta aneurysms. The role of transforming growth factor β (TGFβ) pathway (expression of TGFβR1 and TGFβR2) could be evaluated in BAV stenosis versus BAV insufficiency groups with ascending aorta aneurysms. Forte et al. showed an increased TGFβ and TGFβR2 expression in mildly dilated ascending aortas in BAV stenosis and tricuspid aortic valve stenosis groups and also a decreased TGFβR1 expression only in BAV [2]. The existence of difference or not of the expression of extra domain-A splicing variant of fibronectin in BAV stenosis versus BAV insufficiency groups is an interesting issue as it was shown that its expression was activated in the media of mildly dilated BAV and tricuspid aortic valve (TAV) [2]. Another topic is the evaluation of smooth muscle cell (SMCs) phenotype and orientation in ascending aorta samples (both aortic curvatures) in BAV stenosis versus BAV insufficiency groups as different flow derangements and shear stress anomalies might be observed in these patients. Is there a different pattern of ascending aorta medial remodelling in these groups? Smooth muscle cells switched their phenotype in mildly dilated BAV and tricuspid aortic valve (TAV) [2]. Smoothelin and myocardin mRNAs decreased in all samples from BAV and TAV, with the exception of BAV convexity. There was also a change in orientation of smoothelin-positive SMCs and an increase of α-smooth muscle actin mRNA [2]. The expression of genes that are involved in extracellular matrix remodelling is another field which we could search for differences of expression of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metelloproteinases-2, MMP-9 and other MMPs in BAV stenotic versus BAV insufficiency groups. The MMP-2 mRNA was increased in the convexity of mildly dilated ascending aortas of BAV and TAV groups [2]. Differences in the biosynthesis of collagen and cross-linking in ascending aorta aneurysm of patients with BAV stenosis versus BAV insufficiency is another field of investigation. Are there any differences in collagen turnover in BAV stenosis versus BAV insufficiency groups? It was found that similar collagen turnover rates were observed in dilated and non-dilated aortas of BAV patients [3]. Is the nature of proximal aortic aneurysm (collagen biosynthesis and cross-linking) similar in BAV stenotic and BAV insufficiency groups? Is the collagen network similar in both groups? What about the ratio of hydroxylysyl pyridiholine to lysyl pyridinoline, two distinct forms of collagen cross-linking? Is there any defect in post-translational collagen modification? In dilated aortas from patients with BAV a deficiency was found at the level of lysyl hydroxylase (PLOD1) which showed reduced PLOD1 expression [3]. Could microRNA (miR)-29 expression be involved in the ascending thoracic aorta with aneurysm progression in BAV patients? It was demonstrated that decreased levels of miR-29b in the aortic wall could attenuate aortic aneurysm progression in two different mouse models of abdominal aortic aneurysms [4]. BAV-related ascending aorta dilation represent a potential field of investigation for future research. Conflict of interest: none declared.

Alterations in Aortic Root Geometry in Bicuspid Aortic Insufficiency Versus Stenosis: Implications for Valve Repair

The contribution of aortic annular and root disease in bicuspid aortic valve (BAV) insufficiency remains unclear. We compare the aortic root geometry between BAV stenosis (AS) and insufficiency (AI), before and after AV repair.

Comparison of aortic media changes in patients with bicuspid aortic valve stenosis versus bicuspid valve insufficiency and proximal aortic aneurysm

The aim of this study was to evaluate aortic media changes in bicuspid aortic valve (BAV) patients who underwent aortic valve replacement (AVR) and simultaneous replacement of the proximal aorta for BAV stenosis vs BAV insufficiency. Review of our institutional BAV database identified a subgroup of 79 consecutive BAV patients (mean age 52.3 ± 13 years, 81% men) with BAV stenosis or insufficiency and concomitant proximal aortic dilatation of ≥50 mm who underwent AVR and simultaneous replacement of proximal aorta from 1995 through 2005. All cases of BAV disease and concomitant ascending aortic dilatation of 40-50 mm underwent isolated AVR and therefore were excluded from this analysis. Proximal aortic media elastic fibre loss (EFL) was assessed (graded 0 to 3+) and compared between patients with BAV stenosis (Group I, n = 44) vs BAV insufficiency (Group II, n = 35). Follow-up (690 patient-years) was 100% complete and 9.1 ± 4.6 years long. Mean aortic media EFL was 1.3 ± 0.7 in Group I vs 2.5 ± 0.8 in Group II (P = 0.03). Moderate/severe EFL (i.e. defined as grade 2+/3+) was found in 13 patients (29%) in Group I vs 28 patients (80%) in Group II (P < 0.001). Logistic regression identified BAV insufficiency as the strongest predictor of moderate/severe EFL (OR 9.3; 95% CI 3.2-29.8, P < 0.001). Valve-related event-free survival was 64 ± 8% in Group I vs 93% ± 5% in Group II at 10 years postoperatively (P = 0.05). A total of 4 patients (5%, 3 from Group I and 1 from Group II) underwent redo aortic root surgery for prosthetic valve endocarditis during follow-up. Patients with BAV insufficiency and a proximal aorta of ≥50 mm have a significantly higher rate of moderate/severe EFL as compared to their counterparts with BAV stenosis.

Prospective analysis of transvalvular systolic flow and aortic wall changes in bicuspid aortic valve insufficiency

Methods A total of 76 consecutive patients with BAV disease (57±10 years, 71% male) underwent aortic valve replacement (AVR) ± proximal aortic surgery from January, 2012 through April, 2013. There was a subgroup of 58 (76%) patients with BAV stenosis (Group I), whereas the remaining 18 (14%) patients had isolated BAV insufficiency (Group II). Preoperative cardiac phase-contrast cinemagnetic resonance imaging (MRI) was performed in order to detect the area of maximal flow-induced stress in the proximal aorta. Based on MRI-data, two aortic wall samples i.e., area of the maximal stress (jet-sample) and the opposite aortic wall (control-sample) were collected during surgery. Aortic wall changes were graded based on 7 histological criteria (i.e., each from 0 to 3+) and were summarized in a sum-score. Histological sum-score (0 to 21+) was calculated and compared between samples (i.e., jetvs. control-sample).

Midterm Results of Different Surgical Techniques to Replace Dilated Ascending Aorta Associated With Bicuspid Aortic Valve Disease

This study evaluated effectiveness of three different surgical strategies for treating ascending aorta aneurysm, with or without involvement of the aortic root, associated with bicuspid aortic valve (BAV). Between 2005 and 2011, 150 consecutive patients underwent a Bentall operation in the presence of ascending aorta and aortic root dilation exceeding 45 mm in diameter and malfunctioning BAV (n = 46, group 1); separate aortic valve and ascending aorta replacement in presence of ascending aorta dilation exceeding 45 mm, aortic root of less than 45 mm, and malfunctioning BAV (n = 77, group 2); or ascending aorta replacement, with or without BAV repair, in the presence of ascending aorta dilation exceeding 45 mm, aortic root of less than 45 mm, and normally functioning or mildly insufficient BAV (n = 27, group 3). Compared with groups 2 and 3, group 1 patients were younger and affected by more severe BAV insufficiency and worse left ventricular function. In groups 1, 2, and 3, respectively, operative mortality was 2.1%, 1.3%, and 0%, and 5-year survival was 94% ± 4%, 92% ± 3.4%, and 100%. At 5 years, no patient in any group required reoperation on the ascending aorta or experienced aortic complications. In groups 2 and 3, root dimensions did not increase and were also significantly smaller compared with preoperative measurements (p < 0.05). Aortic regurgitation grade in group 3 (0.5 ± 0.8/4+) did not increase compared with the preoperative grade (0.8 ± 0.9/4+). At midterm follow-up, the Bentall operation remains associated with optimal results for the treatment of BAV, despite a worse preoperative presentation. In presence of a mildly diseased or normal aortic root and normal BAV function at the time of operation, less invasive surgical procedures, BAV-sparing, or repair procedures, appear to offer gratifying results.