Three-year clinical outcomes after transcatheter aortic valve implantation in patients with bicuspid aortic disease: Comparison between self-expanding and balloon-expandable valves.

INTRODUCTION: Bicuspid aortic valve (BAV) stenosis is a complex anatomical scenario for transcatheter aortic valve implantation (TAVI). Favorable short-term clinical outcomes have been reported with TAVI in this setting, but long-term data are scarce. METHODS: We retrospectively included, in a single-center registry, patients with BAV stenosis who underwent TAVI before 2020. We compared patients treated with self-expanding valves (SEV) versus balloon-expandable valves (BEV). The primary endpoint was a composite of all-cause mortality, stroke and need for aortic valve (AV) reintervention at 3 years. Secondary endpoints included each component of the primary endpoint, cardiovascular mortality, permanent pacemaker implantation (PPI) rate, mean gradient and ≥moderate paravalvular leak (PVL) rate. RESULTS: A total of 150 consecutive patients (SEV = 83, BEV = 67) were included. No significant differences were reported between SEV and BEV groups for the primary composite endpoint (SEV 35.9% vs. BEV 32%, p = 0.66), neither for clinical secondary endpoints (all-cause mortality SEV 28.1% vs. BEV 28%, p = 0.988; cardiovascular mortality SEV 14.1% vs. BEV 20%, p = 0.399; stroke SEV 12.5% vs. BEV 6%, p = 0.342; need for AV reintervention SEV 0% vs. BEV 0%; PPI SEV 28.1% vs. BEV 24%, p = 0.620). A lower mean gradient persisted up to 3 years in the SEV group (SEV 8.8 ± 3.8 mmHg vs. BEV 10.7 ± 3.2 mmHg, p = 0.063), while no significant difference was found in the rate of ≥ moderate PVL (SEV 3/30 vs. BEV 0/25, p = 0.242). CONCLUSIONS: In this single center registry, we observed favorable 3-year clinical outcomes in nonselected BAV patients treated with different generation devices, without significant differences between patients receiving SEV or BEV.

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients.

Thoracic aortic aneurysm (TAA) is mainly sporadic and with higher incidence in the presence of a bicuspid aortic valve (BAV) for unknown reasons. The lack of drug therapy to delay TAA progression lies in the limited knowledge of pathophysiology. We aimed to identify the molecular hallmarks that differentiate the aortic dilatation associated with BAV and tricuspid aortic valve (TAV). Aortic vascular smooth muscle cells (VSMCs) isolated from sporadic TAA patients with BAV or TAV were analyzed by mass spectrometry. DNA oxidative damage assay and cell cycle profiling were performed in three independent cohorts supporting proteomics data. The alteration of secreted proteins was confirmed in plasma. Stress phenotype, oxidative stress, and enhanced DNA damage response (increased S-phase arrest and apoptosis) were found in BAV-TAA patients. The increased levels of plasma C1QTNF5, LAMA2, THSB3, and FAP confirm the enhanced stress in BAV-TAA. Plasma FAP and BGN point to an increased inflammatory condition in TAV. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA. The molecular pathways identified support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients, showing specific markers in plasma which may serve to monitor therapy efficacy.

Aortopathy and aortic valve surgery in patients with bicuspid aortic valve with and without raphe.

AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.

Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes.

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

Mechanical behaviors of a new elliptical valve stent in bicuspid aortic valve.

BACKGROUND AND OBJECTIVE: The conventional valve stents that are cylindrical in shape will become elliptical when implanted in bicuspid aortic valve, thereby reducing the durability of the artificial valve. In this study, a new design of valve stent is presented where valve stents have elliptical cross-section at the annulus and it is expected to have better expandability and circle shape during the interaction between the stent and bicuspid aortic valve, thereby extending the durability of artificial valve. METHODS: Finite element method (FEM) is used to study the mechanical behavior of the novel valve stent in the bicuspid aortic valve. The effects of three matching relationship between the ellipticity of the stents and the ellipticity of the annulus (i.e., the ellipticity of the stent is greater than, equal to and less than the annulus ellipticity, respectively) on the mechanical behavior of stent expansion are studied. In addition, the expansion mechanical behavior of the novel valve stent at different implantation depths is also compared. RESULTS: Results indicate that novel valve stent implantation with elliptical features is superior to conventional circular valve stent. When the novel valve stent ellipticity is less than the annulus ellipticity, the ellipticity of the novel valve stent after implantation is smaller than that of the conventional circular valve stent. This indicated that the novel valve stent has better expandability and post-expansion shape, making artificial valve to have better durability. The risk of paravalvular leak after implantation is lowest when the novel valve stent ellipticity is less than annulus ellipticity. When the novel valve stent ellipticity coincides with annulus ellipticity, the aortic wall is subjected to greatest stress. With the increase of implantation depth, the stress on the novel valve stent decrease. CONCLUSIONS: This study might provide insights for improving stent design for bicuspid aortic valve.

Swiss Cheese Heart: A Tale of Multiple Valve Perforations.

Gerbode defect, an anomalous connection between the left ventricle and right atrium, is often congenital but can be acquired or iatrogenically formed. We present an exceedingly rare case of this defect associated with multiple valve perforation in an otherwise healthy patient with bicuspid aortic valve and endocarditis.

Twenty-five years' experience with isolated bicuspid aortic valve repair: impact of commissural orientation.

OBJECTIVES: Repair of the bicuspid aortic valve has evolved in the past 25 years. The aim of this study was to review and analyze the long-term durability of isolated BAV repair with particular focus on commissural orientation (CO). METHODS: All patients who underwent bicuspid aortic valve repair for severe aortic regurgitation between 10/1998 and 12/2022 were included. The study group consists of all patients operated after 2009 ie, since CO modification. The control group includes patients who were operated before 2009. Commissural orientation was classified as symmetric, asymmetric, and very asymmetric. RESULTS: Overall, 594 adult patients (93% male; mean age 42 years) were included. At 15 years, survival was 94.8% (SD : 2.2); freedom from reoperation was 86.8% (SD : 2.3). Freedom from AI≥II was 70.8% (SD : 4.7) at 15 years. Modification of commissural orientation by sinus plication was performed in 200 (33.7%) instances. Using competing risks analysis, the absence of eH measurement (P = 0.018), very asymmetric CO (P = 0.028), the presence of calcification (P < 0.001), the use of pericardial patch (P < 0.001), the use of subcommissural sutures (P < 0.001), and preoperative endocarditis (P = 0.005) were identified as independent predictors for reoperation. Follow-up was 97% complete (4228 patient-years); mean follow-up was 7 years (SD : 5). CONCLUSIONS: Isolated bicuspid aortic valve repair leads to good survival and durability in all morphologic types if cusp repair is guided by effective height, suture annuloplasty is performed, and CO is modified using sinus plication in asymmetrical valves. Very asymmetrical valves may should be treated with a lower threshold for replacement.

Reversible complete atrioventricular block caused by aortic bicuspid valve calcification with severe aortic stenosis: a case report.

Background: The aetiology of secondary complete atrioventricular blocks includes ischaemia, cardiac sarcoidosis, electrolyte imbalance, drug use, rheumatic fever, and infections such as Lyme disease and endocarditis. Diagnosis is important since some of these causes are reversible. Although several studies have reported on aortic valve calcification causing complete atrioventricular blocks, no study has described improvement of complete atrioventricular blocks by removal of the calcification. Case summary: A 42-year-old man with syncope had a Mobitz type II atrioventricular block, an alternating bundle branch block, and severe aortic stenosis. We identified a 10 s paroxysmal complete atrioventricular block with pre-syncope and performed pacemaker implantation. Electrocardiography-gated computed tomography confirmed that the calcification had reached the muscular septum. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed significant FDG uptake with high CT value of calcification in basal interventricular septum. The calcification in the septum was removed carefully, and aortic valve replacement was performed. The atrioventricular conduction capacity improved post-surgery. During the 1-year follow-up, the patient reported dramatic improvement in exercise capacity. We also noted an improvement of <0.1% in the right ventricular pacing burden. Discussion: Complete atrioventricular blocks occur in patients with aortic stenosis accompanied by severe calcification of the aortic valve, which are visualized comprehensively by echocardiography. Electrocardiography-gated computed tomography and FDG-PET enabled detailed evaluation of the extent of calcification and pre- and post-operative tissue inflammation. Hence, we suspected that the calcification in the septum was causing complete atrioventricular block. Moreover, clinicians should recognize that aortic valve calcification with aortic stenosis can cause complete atrioventricular blocks.

Aorta pathology and pregnancy-related risks in adult congenital cardiac disease: does the aorta dilate during pregnancy?

Background: Aortic dilatation and pregnancy are major concerns in women with aortopathy (AOP). This single-centre retrospective analysis focuses on the evolution of aortic diameters during and after pregnancy in women with Marfan syndrome (MS), Turner syndrome (TS) and bicuspid aortic valve (BAV) aortopathy. Methods and results: Thirty-eight women who had one or more single pregnancies were included. The ascending aorta was measured during pregnancy and postpartum. During pregnancy, a significant increase of diameters of the sinus aortae (median 1.4 mm; [-1.3; 3.8]) and ascending aorta (median 2.1 mm; [0.0; 4.0]) was noted. Systemic hypertension gives dilation of the aorta, but it did not influence the overall trajectory during pregnancy. Conclusion: Significant aortic dilatation is noted during pregnancy in women with underlying AOP, even persisting in the long term. Pre-existing systemic hypertension is associated with larger aortic diameters prior to pregnancy. More research on a larger study population however is needed.

Systematic review of cardiovascular neurocristopathy-contemporary insights and future perspectives.

Introduction: Neural crest cells (NCCs) are multipotent and are attributed to the combination of complex multimodal gene regulatory mechanisms. Cardiac neural crest (CNC) cells, originating from the dorsal neural tube, are pivotal architects of the cardio-neuro-vascular domain, which orchestrates the embryogenesis of critical cardiac and vascular structures. Remarkably, while the scientific community compiled a comprehensive inventory of neural crest derivatives by the early 1980s, our understanding of the CNC's role in various cardiovascular disease processes still needs to be explored. This review delves into the differentiation of NCC, specifically the CNC cells, and explores the diverse facets of non-syndromic cardiovascular neurocristopathies. Methods: A systematic review was conducted as per the PRISMA Statement. Three prominent databases, PubMed, Scopus, and Embase, were searched, which yielded 1,840 studies. We excluded 1,796 studies, and the final selection of 44 studies formed the basis of this comprehensive review. Results: Neurocristopathies are a group of genetic disorders that affect the development of cells derived from the NC. Cardiovascular neurocristopathy, i.e., cardiopathy and vasculopathy, associated with the NCC could occur in the form of (1) cardiac septation disorders, mainly the aortico-pulmonary septum; (2) great vessels and vascular disorders; (3) myocardial dysfunction; and (4) a combination of all three phenotypes. This could result from abnormalities in NCC migration, differentiation, or proliferation leading to structural abnormalities and are attributed to genetic, familial, sporadic or acquired causes. Discussion: Phenotypic characteristics of cardiovascular neurocristopathies, such as bicuspid aortic valve and thoracic aortic aneurysm, share a common embryonic origin and are surprisingly prevalent in the general population, necessitating further research to identify the underlying pathogenic and genetic factors responsible for these cardiac anomalies. Such discoveries are essential for enhancing diagnostic screening and refining therapeutic interventions, ultimately improving the lives of individuals affected by these conditions.

Region-specific delamination strength of ascending thoracic aortic aneurysm of elderly hypertensive patients with bicuspid and tricuspid aortic valves.

Both ageing and hypertension are clinical factors that may lead to a higher propensity for dissection or rupture of ascending thoracic aortic aneurysms (ATAAs). This study sought to investigate effect of valve morphology on regional delamination strength of ATAAs in the elderly hypertensive patients. Whole fresh ATAA samples were harvested from 23 hypertensive patients (age, 71 ± 8 years) who underwent elective aortic surgery. Peeling tests were performed to measure region-specific delamination strengths of the ATAAs, which were compared between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The regional delamination strengths of the ATAAs were further correlated with patient ages and aortic diameters for BAV and TAV groups. In the anterior and right lateral regions, the longitudinal delamination strengths of the ATAAs were statistically significantly higher for BAV patients than TAV patients (33 ± 7 vs. 23 ± 8 mN/mm, p = 0.01; 30 ± 7 vs. 19 ± 9 mN/mm, p = 0.02). For both BAV and TAV patients, the left lateral region exhibited significantly higher delamination strengths in both directions than the right lateral region. Histology revealed that disruption of elastic fibers in the right lateral region of the ATAAs was more severe for the TAV patients than the BAV patients. A strong inverse correlation between longitudinal delamination strength and age was identified in the right lateral region of the ATAAs of the TAV patients. Results suggest that TAV-ATAAs are more vulnerable to aortic dissection than BAV-ATAAs for the elderly hypertensive patients. Regardless of valve morphotypes, the right lateral region may be a special quadrant which is more likely to initiate dissection when compared with other regions.

Left atrial dysfunction in bicuspid aortic valve patients with severe aortic stenosis is associated with post-operative atrial fibrillation following aortic valve replacement.

Aims: To investigate (i) the association between pre-operative left atrial (LA) reservoir strain and post-operative atrial fibrillation (AF) and (ii) the incidence of post-operative ischaemic stroke events separately in bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients after surgical aortic valve replacement for isolated severe aortic stenosis (AS). Methods and results: We prospectively enrolled 227 patients (n = 133 BAV and n = 94 TAV) with isolated severe AS scheduled for aortic valve replacement. A comprehensive intra- and inter-observer validated pre-operative echocardiogram with an analysis of LA reservoir strain was performed. Post-operative AF was defined as a sustained (>30 s) episode of AF or atrial flutter. The timing of neurological events was defined in accordance with the Valve Academic Research Consortium-3 criteria for stroke. Post-operative AF occurred in 114 of 227 patients (50.2%), with no difference between BAV and TAV patients (48.1 vs. 53.1%, P = 0.452). Persisting post-operative AF at discharge was more frequent in BAV patients (29.7 vs. 8.0%, P = 0.005). Pre-operative LA reservoir strain was independently associated with post-operative AF (odds ratio = 1.064, 95% confidence interval 1.032-1.095, P < 0.001), with a significant interaction between LA reservoir strain and aortic valve morphology (Pinteraction = 0.002). The cumulative transient ischemic attack (TIA)/stroke incidence during follow-up was significantly higher in BAV patients (19.1 vs. 5.8% at 5 years). Conclusion: Pre-operative LA function was associated with post-operative AF after aortic valve replacement in BAV AS patients, while post-operative AF in TAV AS patients likely depends on transient post-operative alterations and traditional cardiovascular risk factors. TIA/stroke during follow-up was more common in BAV AS patients.

Patient-specific analysis of bicuspid aortic valve hemodynamics using a fully coupled fluid-structure interaction model.

Bicuspid aortic valve (BAV), the most common congenital heart disease, is prone to develop significant valvular dysfunction and aortic wall abnormalities such as ascending aortic aneurysm. Growing evidence has suggested that abnormal BAV hemodynamics could contribute to disease progression. In order to investigate BAV hemodynamics, we performed 3D patient-specific fluid-structure interaction (FSI) simulations with fully coupled blood flow dynamics and valve motion throughout the cardiac cycle. Results showed that the hemodynamics during systole can be characterized by a systolic jet and two counter-rotating recirculation vortices. At peak systole, the jet was usually eccentric, with asymmetric recirculation vortices and helical flow motion in the ascending aorta. The flow structure at peak systole was quantified using the vorticity, flow rate reversal ratio and local normalized helicity (LNH) at four locations from the aortic root to the ascending aorta. The systolic jet was evaluated with the peak velocity, normalized flow displacement, and jet angle. It was found that peak velocity and normalized flow displacement (rather than jet angle) gave a strong correlation with the vorticity and LNH in the ascending aorta, which suggests that these two metrics could be used for clinical noninvasive evaluation of abnormal blood flow patterns in BAV patients.

Prognostic Implications of Left Atrial Strain in Bicuspid Aortic Valve With Chronic Aortic Regurgitation.

BACKGROUND: Left atrial reservoir strain (LARS) is a novel imaging biomarker of left ventricular diastolic dysfunction. This study aimed to examine the prognostic implications of LARS in patients with bicuspid aortic valve and significant (moderate-severe to severe) aortic regurgitation. METHODS AND RESULTS: A total of 220 patients with bicuspid aortic valve and significant aortic regurgitation were prospectively enrolled in our study. LARS and left ventricular global longitudinal strain were derived from speckle-tracking echocardiography. The end point was a composite of all-cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The threshold value of LARS <24% was used to identify impaired left atrial mechanics based on prior results. During a median follow-up of 364 (interquartile range, 294-752) days, 46 patients (20.9%) reached the composite end points. On multivariable Cox analysis, impaired LARS (adjusted hazard ratio, 2.08 [95% CI, 1.05-4.11]; P=0.036) was a statistically significant predictor of composite end points after adjustment for other statistically significant predictors. Finally, adding impaired LARS to other statistically significant predictors (New York Heart Association functional class and left ventricular global longitudinal strain) significantly improved the global χ2 (from 32.19 to 36.56; P=0.037) and reclassification (continuous net reclassification index=0.55; P<0.001) of the prediction model. CONCLUSIONS: In patients with bicuspid aortic valve and significant aortic regurgitation, the impairment of LARS is a strong independent prognostic predictor and confers incremental prognostic utility over clinical and other echocardiographic parameters. These findings suggest that LARS could be considered in risk stratification for such populations.

Multiyear Interval Changes in Aortic Wall Shear Stress in Patients with Bicuspid Aortic Valve Assessed by 4D Flow MRI.

BACKGROUND: In patients with bicuspid aortic valve (BAV), 4D flow MRI can quantify regions exposed to abnormal aortic hemodynamics, including high wall shear stress (WSS), a known stimulus for arterial wall dysfunction. However, the long-term multiscan reproducibility of 4D flow MRI-derived hemodynamic parameters is unknown. PURPOSE: To investigate the long-term stability of 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps in patients with BAV undergoing multiyear surveillance imaging. STUDY TYPE: Retrospective. POPULATION: 20 BAV patients (mean age 48.4 ± 13.9 years; 14 males) with five 4D flow MRI scans, with intervals of at least 6 months between scans, and 125 controls (mean age: 50.7 ± 15.8 years; 67 males). FIELD STRENGTH/SEQUENCE: 1.5 and 3.0T, prospectively ECG and respiratory navigator-gated aortic 4D flow MRI. ASSESSMENT: Automated AI-based 4D flow analysis pipelines were used for data preprocessing, aorta 3D segmentation, and quantification of ascending aorta (AAo) peak velocity, peak systolic WSS, and heatmap-derived relative area of elevated WSS compared to WSS ranges in age and sex-matched normative control populations. Growth rate was derived from the maximum AAo diameters measured on the first and fifth MRI scans. STATISTICAL TESTS: One-way repeated measures analysis of variance. P < 0.05 indicated significance. RESULTS: One hundred 4D flow MRI exams (five per patient) were analyzed. The mean total follow-up duration was 5.5 ± 1.1 years, and the average growth rate was 0.3 ± 0.2 mm/year. Peak velocity, peak systolic WSS, and relative area of elevated WSS did not change significantly over the follow-up period (P = 0.64, P = 0.69, and P = 0.35, respectively). The patterns and areas of elevated WSS demonstrated good reproducibility on semiquantitative assessment. CONCLUSION: 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps showed good multiyear and multiscan stability in BAV patients with low aortic growth rates. These findings underscore the reliability of these metrics in monitoring BAV patients for potential risk of dilation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Coarctation of Aorta With Tricuspid Aortic Valve Is Not Associated With Ascending Aortic Aneurysm.

BACKGROUND: Aortic aneurysm is common in patients with coarctation of aorta (COA), but it is unclear whether the risk of aortic aneurysms is due to COA or related to the presence of other risk factors such as bicuspid aortic valve (BAV) and hypertension. OBJECTIVES: The purpose of this study was to assess the relationship among COA, BAV, and thoracic aortic aneurysms. METHODS: A total of 867 patients with COA (COA group) were matched 1:1:1 to 867 patients with isolated BAV (BAV group) and 867 patients without structural heart disease (SHD) (no-SHD group). The COA group was further subdivided into a COA+BAV subgroup (n = 304 [35%]), and COA with tricuspid aortic valve (TAV) (COA+TAV subgroup [n = 563 (65%)]). Aortic dimensions were assessed at baseline and at 3, 5, and 7 years. RESULTS: Compared with the no-SHD group, the COA+BAV subgroup had larger aortic root diameter (37 mm [Q1-Q3: 30-43 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001) and mid ascending aorta dimeter (34 mm [Q1-Q3: 29-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P = 0.008). Similarly, the BAV group had larger aortic root diameter (37 mm [Q1-Q3: 30-42 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001), and mid ascending aorta dimeter (35 mm [Q1-Q3: 30-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P < 0.001). Compared with the COA+TAV subgroup, the COA+BAV subgroup and BAV group were associated with larger aortic root and mid ascending aorta diameter at baseline and follow-up. The risk of acute aortic complications was low in all groups. CONCLUSIONS: These findings suggest that BAV (and not COA) was associated with ascending thoracic aorta dimensions, and that patients with COA+TAV were not at a greater risk of developing ascending aortic aneurysms as compared with patients without SHD.