Bicuspid aortic valve and aortopathy: novel prognostic predictors for the identification of high-risk patients

2020 ◽  
Author(s):  
Luca Longobardo ◽  
Scipione Carerj ◽  
Alessandra Bitto ◽  
Maurizio Cusmà-Piccione ◽  
Maria Ludovica Carerj ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Surgical Treatment ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Primary Endpoint ◽  
Cox Regression ◽  
Aortic Surgery ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Cox Regression Analysis

Abstract Aims Bicuspid aortic valve (BAV) may be complicated by aortic aneurysms and dissection. This study aimed to evaluate the prognostic efficacy of markers from cardiac imaging, as well as genetic and new biomarkers, to early predict aortic complications. Methods and results We re-evaluated after a mean time of 48 ± 11 months 47 BAV patients who had undergone previous echocardiography for evaluation of aortic stiffness and 2D aortic longitudinal strain (LS) (by speckle-tracking analysis), and who had given a blood sample for the assessment of a single-nucleotide polymorphism of elastin gene (ELN rs2 071307) and quantification of elastin soluble fragments (ESF). Surgical treatment of aortic aneurysm/dissection was the primary endpoint, and an aortic dimension increase (of one or more aortic segments) ≥1 mm/year was the secondary endpoint. Nine patients underwent surgical treatment of ascending aorta (AA) aneurysms. Out of the 38 patients who did not need surgical intervention, 16 showed an increase of aortic root and/or AA dimension ≥1 mm/year. At multivariate Cox regression analysis, an impaired AA LS was an independent predictor of aortic surgery [P = 0.04; hazard ratio (HR) 0.961; 95% confidence interval (CI) 0.924–0.984] and aortic dilatation (P = 0.007; HR 0.960; 95% CI 0.932–0.989). An increased quantity of ESF was correlated (P = 0.015) with the primary endpoint at univariate Cox regression analysis but it did not keep statistical significance at multivariate analysis. Conclusion In BAV patients, impairment of elastic properties of the AA, as assessed by 2D LS, is an effective predictor of aortic complications.

Abstract 19123: Elevated Growth and Differentiation Factor 15 (GDF15) Levels Predict Outcome in Patients With Severe Aortic Stenosis Undergoing Tavi

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Nora Krau ◽  
Sandra Freitag-Wolf ◽  
Doreen Brehm ◽  
Rainer Petzina ◽  
Georg Lutter ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Aortic Valve ◽  
Risk Stratification ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Severe Aortic Stenosis ◽  
Statistical Significance ◽  
Cox Regression Analysis ◽  
Negative Outcome

Background: GDF15 belongs to the transforming growth factor superfamily and has a significant role in regulating inflammatory and apoptotic pathways. GDF15 is an emerging biomarker for risk stratification in cardiovascular disease. Here we analyze its prognostic value in patients with severe symptomatic aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods and Results: We prospectively enrolled 217 patients undergoing TAVI (using Edwards Sapien XT prostheses) at our institution over a continuous period of 35 month (2/2011-12/2013). All patients were available for complete follow up. Clinical parameters were determined before the procedure, biomarkers (GDF15 & NTproBNP) were measured before, 3 and 7 days after TAVI. The primary endpoint was survival time, all available prognostic factors were studied by Cox regression analysis with backward selection based on the likelihood ratio criteria. At median follow-up of 349 d (Q1-Q3 106-660d), a total of n=66 deaths occurred. 30d mortality was 6.9%. Mean age was 81.8 years (± 6.0 y) and 55.8% were females. Mean log. Euroscore (ES) was 25.4% (± 17.2%). Median preprocedural GDF15 values were 2256 pg/ml (Q1-Q3 1585.5-3082.0). In univariate analyses, increased GDF15 levels (upper quartile compared to lower three quartiles) revealed a HR of 2.4 (CI 1.5-3.9, p<0.001) for adverse outcome. In addition, also log. ES (p= 0.001), log. ES II (p=0.018), STS-Score (p=0.019), NTproBNP (p=0.037) and atrial fibrillation (p=0.02) demonstrated statistical significance for negative outcome. A multivariate Cox regression analysis including these factors and postprocedural aortic regurgitation, demonstrated that elevated GDF15 had a HR of 2.104 (CI 1.3-3.5; p=0.003) for negative outcome in patients undergoing TAVI, while elevated NTproBNP had HR of 1.412 (CI 0.8-2.4; p=0.212). Moreover, this analysis also revealed the log. ES as an independent risk factor (HR of 2.211, CI 1.3-3.7; p= 0.002). Conclusion: Increased GDF15 levels are associated with a poor prognosis in patients undergoing TAVI. Furthermore, GDF15 showed to be superior to the established biomarker NTproBNP in risk stratification of patients undergoing TAVI providing additional prognostic information.

scholarly journals Differences in Aortopathy in Patients with a Bicuspid Aortic Valve with or without Aortic Coarctation

2020 ◽  
Vol 9 (2) ◽  
pp. 290
Author(s):  
Anthonie Duijnhouwer ◽  
Allard van den Hoven ◽  
Remy Merkx ◽  
Michiel Schokking ◽  
Roland van Kimmenade ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Dissection ◽  
Bicuspid Aortic Valve ◽  
Aortic Coarctation ◽  
Care Center ◽  
Aortic Surgery ◽  
Tertiary Care ◽  
Aortic Diameter ◽  
Aortic Dilatation ◽  
Significant Difference

Objective: The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is assumed to be associated with a higher risk of ascending aortic dilatation and type A dissection, and current European Society of Cardiology (ESC) guidelines advise therefore to operate at a lower threshold in the presence of CoA. The aim of our study is to evaluate whether the coexistence of CoA in BAV patients is indeed associated with a higher risk of ascending aortic events (AAE). Methods: In a retrospective study, all adult BAV patients visiting the outpatient clinic of our tertiary care center between February 2003 and February 2019 were included. The primary end point was an ascending aortic event (AAE) defined as ascending aortic dissection/rupture or preventive surgery. The secondary end points were aortic dilatation and aortic growth. Results: In total, 499 BAV patients (43.7% female, age 40.3 ± 15.7 years) were included, of which 121 (24%) had a history of CoA (cBAV). An aortic event occurred in 38 (7.6%) patients at a mean age of 49.0 ± 13.6 years. In the isolated BAV group (iBAV), significantly more AAE occurred, but this was mainly driven by aortic valve dysfunction as indication for aortic surgery. There was no significant difference in the occurrence of dissection or severely dilated ascending aorta (>50 mm) between the iBAV and cBAV patients (p = 0.56). The aortic diameter was significantly smaller in the cBAV group (30.3 ± 6.9 mm versus 35.7 ± 7.6 mm; p < 0.001). The median aortic diameter increase was 0.23 (interquartile range (IQR): 0.0–0.67) mm/year and was not significantly different between both groups (p = 0.74). Conclusion: Coexistence of CoA in BAV patients was not associated with a higher risk of aortic dissection, preventive aortic surgery, aortic dilatation, or more rapid aorta growth. This study suggests that CoA is not a risk factor in BAV patients, and the advice to operate at lower diameter should be reevaluated.

scholarly journals Bicuspid Aortic Valve Disease and Ascending Aortic Aneurysms: Gaps in Knowledge

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Katie L. Losenno ◽  
Robert L. Goodman ◽  
Michael W. A. Chu
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Valve Disease ◽  
Aortic Aneurysms ◽  
Valve Disease ◽  
Cardiac Anomaly ◽  
Aortic Dilatation ◽  
Congenital Cardiac Anomaly ◽  
Valvular Stenosis ◽  
Ongoing Surveillance

The bicuspid aortic valve is the most common congenital cardiac anomaly in developed nations. The abnormal bicuspid morphology of the aortic valve results in valvular dysfunction and subsequent hemodynamic derangements. However, the clinical presentation of bicuspid aortic valve disease remains quite heterogeneous with patients presenting from infancy to late adulthood with variable degrees of valvular stenosis and insufficiency and associated abnormalities including aortic coarctation, hypoplastic left heart structures, and ascending aortic dilatation. Emerging evidence suggests that the heterogeneous presentation of bicuspid aortic valve phenotypes may be a more complex matter related to congenital, genetic, and/or connective tissue abnormalities. Optimal management of patients with BAV disease and associated ascending aortic aneurysms often requires a thoughtful approach, carefully assessing various risk factors of the aortic valve and the aorta and discerning individual indications for ongoing surveillance, medical management, and operative intervention. We review current concepts of anatomic classification, pathophysiology, natural history, and clinical management of bicuspid aortic valve disease with associated ascending aortic aneurysms.

Fluid Structural Interaction of a Patient Specific Congenital Bicuspid Aortic Valve

2012 ◽  
Author(s):  
V. Govindarajan ◽  
H. S. Udaykumar ◽  
S. Vigmostad ◽  
M. M. Levack ◽  
J. H. Gorman ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Root ◽  
Aortic Aneurysms ◽  
Patient Specific ◽  
Aortic Dilatation ◽  
Structural Interaction ◽  
Aortic Pathology ◽  
Specific Geometry ◽  
Opening Phase

Congenital Bicuspid Aortic Valve (BAV) is a valvular anomaly where a patient is born with a valve with two leaflets instead of a normal tri-leaflet valve. It has also been reported that BAVs are prone to progressive calcification and also other complications such as ascending aortic dilatation, dissection and rupture [1]. The geometrical variations with the BAV may be a factor in altering the deformation and stresses on the leaflets resulting in calcification of the leaflets earlier than with normal tri-leaflet aortic valves. Altered flow patterns past BAV into the ascending aorta can also be anticipated. Analysis of flow dynamics during the opening phase, and the resultant fluid forces on the aortic root could improve our understanding of aortic aneurysms and dissections observed in patients with BAV [2]. In this study, the valvular deformation and the flow across a patient-specific BAV and root are simulated using the method of fluid structural interaction analysis. The patient-specific geometry is obtained employing 3D ultrasound images segmented as point cloud data and surfaces are constructed with commercial software GAMBIT using NURBS based connectivity. The opening phase of the valve is simulated under flow with physiological Reynolds number and with realistic material properties for the leaflets and the aortic root. Such an analysis on the dynamics of BAV with patient-specific geometry may be a useful tool in stratifying BAV patients that may be at risk in developing valvular and ascending aortic pathology.

scholarly journals Bicuspid Aortic Valve: Role of Multiple Gene Variants in Influencing the Clinical Phenotype

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Sticchi ◽  
Rosina De Cario ◽  
Alberto Magi ◽  
Sabrina Giglio ◽  
Aldesia Provenzano ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Root ◽  
Rare Variants ◽  
Aortic Surgery ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Aortic Dilatation ◽  
Reduced Penetrance ◽  
Next Generation Sequencing Ngs

Background. Bicuspid aortic valve (BAV) is a common congenital heart defect with increased prevalence of aortic dilatation and dissection. BAV has an autosomal dominant pattern of inheritance with reduced penetrance and variable expressivity. BAV has been described as an isolated trait or associated with other clinical manifestations in syndromic conditions. Identification of a syndromic condition in a BAV patient is clinically relevant in order to personalize indication to aortic surgery. We aimed to point out how genetic diagnosis by next-generation sequencing (NGS) can improve management of a patient with complex BAV clinical picture. Methods and Results. We describe a 45-year-old Caucasian male with BAV, thoracic aortic root and ascending aorta dilatation, and connective features evocative but inconclusive for clinical diagnosis of Marfan syndrome (MFS). Targeted (91 genes) NGS was used. Proband genetic variants were investigated in first-degree relatives. Proband carried 5 rare variants in 4 genes: FBN1(p.Asn542Ser and p.Lys2460Arg), NOTCH1(p.Val1739Met), LTBP1(p.Arg1330Gln), and TGFBR3(p.Arg423Trp). The two FBN1 variants were inherited in cis by the mother, showing systemic features evocative of MFS, but with a milder phenotype than that observed in the proband. Careful clinical observation along with the presence of the FBN1 variants allowed diagnosis of MFS in the proband and in his mother. NOTCH1 variant was found in mother and brother, not exhibiting BAV, thus not definitely supporting/excluding association with BAV. Interestingly, the proband, his brother and father, all showing root dilatation, and his sister, with upper range aortic root dimension, were carriers of a TGFBR3 variant. LTBP1 might also modulate the vascular phenotype. Conclusions. Our results underline the usefulness of NGS together with family evaluation in diagnosis of patients with monogenic traits and overlapping clinical manifestations due to contribution of the same genes and/or presence of comorbidities determined by different genes.

Ascending aorta mechanics in bicuspid aortopathy: controversy or fact?

2020 ◽  
pp. 021849232092873
Author(s):  
Dimitrios C Iliopoulos ◽  
Dimitrios P Sokolis
Keyword(s):  
Mechanical Properties ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Aged Patients ◽  
Thoracic Aortic Aneurysms ◽  
Maximal Diameter ◽  
Sole Criterion

Bicuspid aortic valve is the most common congenital cardiovascular defect, often associated with proximal aortic dilatation, and the ideal management strategy is debated. The inconsistency in previous and present guideline recommendations emphasizes the insufficiency of the maximal diameter as the sole criterion for prophylactic repair. Our ability to guide clinical decisions may improve through an understanding of the mechanical properties of ascending thoracic aortic aneurysms in bicuspid compared to tricuspid aortic valve patients and non-aneurysmal aortas, because dissection and rupture are aortic wall mechanical failures. Such an understanding of the mechanical properties has been attempted by several authors, and this article addresses whether there is a controversy in the accumulated knowledge. The available mechanical studies are briefly reviewed, discussing factors such as age, sex, and the region of mechanical examination that may be responsible for the lack of unanimity in the reported findings. The rationale for acquiring layer-specific properties is presented along with the main results from our recent study. No mechanical vulnerability of ascending thoracic aortic aneurysms was evidenced in bicuspid aortic valve patients, corroborating present conservative guidelines concerning the management of bicuspid aortopathy. Weakening and additional vulnerability was evidenced in aged patients and those with coexisting valve pathology, aortic root dilatation, hypertension, and hyperlipidemia. Discussion of these results from age- and sex-matched subjects, accounting for the region- and layer-specific aortic heterogeneity, in relation to intact wall results and histologic confirmation, helps to reconcile previous findings and affords a universal interpretation of ascending aorta mechanics in bicuspid aortopathy.

Abstract 15097: Altered TGFβ Signalling Effector Molecules Contribute to Bicuspid Aortic Valve-associated Thoracic Aortopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Candice L Dilworth ◽  
Francesca Sadnick ◽  
Sari Padang ◽  
Yaxin Lu ◽  
Elizabeth N Robertson ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Aneurysms ◽  
Extra Cellular Matrix ◽  
Matrix Metalloproteinase 2 ◽  
Compensatory Mechanism ◽  
Aortic Dilatation ◽  
Matrix Degradation ◽  
Tgfβ Signalling ◽  
Cellular Matrix

Upregulated TGFβ signalling plays a key role in mediating congenital thoracic aortic aneurysms (TAA), and has been implicated in bicuspid aortic valve-associated TAA (BAV-TAA). TGFβ is normally stored within the extra-cellular matrix via sequestration proteins bound to the microfibrillar protein, fibrillin. TGFβ is released in response to changes in these sequestration proteins, allowing TGFβ to exert its signalling effects. We hypothesised that in BAV-TAA the upregulation of TGFβ signalling will pathologically alter effector molecule expression, causing matrix degradation and altered TGFβ sequestration. Immunohistochemistry was used to quantify protein expression in aortic tissue from 8 human BAV-TAA and 6 normal controls. In BAV-TAA, TGFβ expression was elevated in all layers (2.5:1; p<0.05), particularly in the adventitia (3.4:1; p<0.001). Microfibril-associated glycoprotein-1 (MAGP-1), which promotes TGFβ release, was elevated (2:1; p<0.03), while latent TGFβ binding protein-1 (LTBP-1), which promotes TGFβ sequestration, was decreased (0.3:1; p=0.03). Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression was elevated (2.6:1; p<0.005, 1.5:1; p<0.05, respectively), and MMP-3 expression was decreased (0.5:1; p<0.05). Fibrillin-1 expression was not altered. The observed changes in TGFβ sequestration proteins will increase unbound TGFβ, leading to upregulation of downstream signalling. The elevated levels of MMP-2 and MMP-9 mediate pathological matrix remodelling, leading to aortic dilatation. The paradoxical decrease in MMP-3 may represent a compensatory mechanism that attempts to reduce overall pathological MMP activity, in order to limit damage to the aortic wall. In conclusion, in BAV-TAA excessive TGFβ signalling is potentiated by reduced TGFβ sequestration, causing extra-cellular matrix degradation by MMPs. This supports the rationale for the use of angiotensin II receptor blockers in BAV-TAA.

scholarly journals Low systemic arterial compliance is associated with increased cardiovascular morbidity and mortality in aortic valve stenosis

Heart ◽  
2019 ◽  
Vol 105 (19) ◽  
pp. 1507-1514 ◽  
Author(s):  
Edda Bahlmann ◽  
Dana Cramariuc ◽  
Sahrai Saeed ◽  
John B Chambers ◽  
Christoph A Nienaber ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Cox Regression ◽  
Arterial Compliance ◽  
Cardiovascular Morbidity ◽  
Morbidity And Mortality ◽  
Cox Regression Analysis ◽  
Cardiovascular Morbidity And Mortality ◽  
All Cause Mortality

ObjectiveLower systemic arterial compliance (SAC) is associated with increased cardiovascular morbidity and mortality in hypertension, but this has not been assessed in a prospective study in aortic valve stenosis (AS).MethodsData from 1641 patients (38% women) with initially asymptomatic mild-moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study was used. Median follow-up was 4.3 years. SAC was assessed from Doppler stroke volume index to central pulse pressure ratio and considered low if ≤0.64 mL/m², corresponding to the lower tertile in the population. The association of SAC with outcome was assessed in Cox regression analysis and reported as HR and 95% CI.ResultsLow SAC at baseline was characterised by older age, female sex, hypertension, obesity, presence of a small aortic root, lower mean aortic gradient and more severe AS by effective aortic valve area (all p<0.01). In Cox regression analysis adjusting for factors, low SAC was associated with higher HRs for cardiovascular death (HR 2.13(95% CI 1.34 to 3.40) and all-cause mortality (HR 1.71(95% CI 1.23 to 2.38)), both p=0.001). The results did not change when systolic or diastolic blood pressure, other measures of AS severity or presence of discordantly graded AS were included in subsequent models. Presence of low SAC did not improve mortality prediction in reclassification analysis.ConclusionsIn patients with AS without diabetes and known cardiovascular disease, but a high prevalence of hypertension, low SAC was associated with higher cardiovascular and all-cause mortality independent of well-known prognosticators.Trial registration numberNCT00092677; Post-results.

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