Bicuspid Aortic Valve Research Articles

Genetic investigation and diagnosis in adults with congenital heart disease with or without structural or neurodevelopmental comorbidity: a retrospective chart review.

Genetic evaluation is indicated for individuals with congenital heart disease (CHD), especially if extracardiac anomalies are also present. Timely recognition of genetic diagnoses can facilitate medical management and as well as provide assessment of reproductive risk. At least 20% of the pediatric population with CHD has a syndrome or genetic diagnosis. Further, at least 30% have extracardiac congenital malformations and/or neurodevelopmental differences (NDD), and this is known to increase the likelihood of a genetic/syndromic diagnosis. However, little is known regarding whether these statistics also apply to the current population of adults living with CHD, many of whom were born prior to currently available genetic testing. The primary aim of this study was to determine the prevalence of documented genetic and syndromic diagnoses in a cohort of adults with CHD followed by a dedicated adult CHD (ACHD) clinic. The secondary aims were to describe genetic testing and genetic referral patterns in this population and identify the presence of extracardiac comorbidities which are known to be indicative of an underlying genetic diagnosis in the pediatric CHD population. To answer these questions, we performed a retrospective chart review on a sample of adults with CHD (excluding those with isolated bicuspid aortic valve) seen at Cincinnati Children's Hospital in the ACHD clinic between 2010-2021. Among 233 adult CHD patients, 36 (14%) had a documented genetic or syndromic diagnosis but only 29 (13.7%) had received genetic testing, while 27 (11.6%) had received genetic referrals. Furthermore, of 170 patients without any documented genetics related care (defined as genetic testing, genetic referrals, or genetic diagnosis), 35 (20%) had at least one congenital and/or neurodevelopmental comorbidity. Factors associated with individuals having received genetics related care included younger age (<40), male sex, and presence of extracardiac comorbidities. Our results indicate important gaps in genetics-related care for adults living with CHD. The subset of our cohort with congenital and/or neurodevelopmental comorbidities who received no genetic-related care, represent a population of adults with CHD who may have unrecognized genetic diagnoses.

Aortic valve function and aortic dimensions in obese and overweight patients with bicuspid aortic valve.

Bicuspid aortic valve is the most common CHD and commonly associated with activity restrictions that may lead to a sedentary lifestyle known to increase obesity risk. It is unknown whether obesity is associated with changes in aortic dimensions or aortic valve function in young people with bicuspid aortic valve. This study investigates whether overweight and obese children with bicuspid aortic valve have worse aortic valve function or increased aortic dimensions compared to healthy weight children with bicuspid aortic valve. This was a single centre retrospective cohort study comprised of patients 5 to 25 years old with a diagnosis of bicuspid aortic valve between 1 January, 2019 and 31 December, 2020. Patients were classified as healthy weight or overweight/obese. Values for aortic dimensions as well as peak and mean aortic valve gradients were obtained from echocardiogram reports. About 251 patients were analysed. Demographics were similar between groups. When indexed to height, the aortic valve annulus (1.28 ± 0.14 vs. 1.34 ± 0.15, p = 0.001) and sinotubular junctions (1.44 ± 0.21 vs. 1.49 ± 0.24, p = 0.038) were larger in the overweight/obese group, with no differences in aortic root or ascending aorta sizes. The obese/overweight group had a higher peak aortic valve gradient (23.03 ± 1.64 mmHg vs. 16.17 ± 1.55 mmHg, p = 0.003) compared to the healthy weight group. Healthy weight patients did not have larger aortic dimensions compared to the overweight/obese patients. There was evidence of worsening aortic valve stenosis in overweight/obese patients compared to those at a healthy weight.

Bicuspid Valve Aortopathy: Is It Reasonable to Define a Different Surgical Cutoff Based on Different Aortic Wall Mechanical Properties Compared to Those of the Tricuspid Valve?

In this study, we examined and compared ex vivo mechanical properties of aortic walls in patients with bicuspid (BAV) and tricuspid (TAV) aortic valve aortopathy to investigate if the anatomical peculiarities in the BAV group are related to an increased frailty of the aortic wall and, therefore, if a different surgical cutoff point for ascending aortic replacement could be reasonable in such patients. Ultimate stress tests were performed on fresh aortic wall specimens harvested during elective aortic surgery in BAV (n. 33) and TAV (n. 77) patients. Three mechanical parameters were evaluated at the failure point, under both longitudinal and circumferential forces: the peak strain (Pstr), peak stress (PS), and maximum elastic modulus (EM). The relationships between the three mechanical parameters and preoperative characteristics were evaluated, with a special focus on evaluating potential risk factors for severely impaired mechanical properties, cumulatively and comparatively (BAV vs. TAV groups). The patient populations were inhomogeneous, as BAV patients reached surgical indication, according to the maximum aortic dilatation, at a younger age (58 ± 15 vs. 64 ± 13; p = 0.0294). The extent of the maximum aortic dilatation was, conversely, similar in the two groups (52 ± 4 vs. 54 ± 7; p = 0.2331), as well as the incidences of different phenotypes of aortic dilatation (with the ascending aorta phenotype being the most frequent in 81% and 66% of the BAV and TAV patients, respectively (p = 0.1134). Cumulatively, the mechanical properties of the aortic wall were influenced mainly by the orientation of the force applied, as both PS and EM were impaired under longitudinal stress. An age of >66 and a maximum dilatation of >52 mm were shown to predict severe Pstr reduction in the overall population. Comparative analysis revealed a trend of increased mechanical properties in the BAV group, regardless of the position, the force orientation, and the phenotype of the aortic dilatation. BAV aortopathy is not correlated with impaired mechanical properties of the aortic wall as such. Different surgical cutoff points for BAV aortopathy, therefore, seem to be unjustified. An age of >66 and a maximum aortic dilatation of >52 mm, however, seem to significantly influence the mechanical properties of the aortic wall in both groups. These findings, therefore, could suggest the need for more accurate monitoring and evaluation in such conditions.

7768 Hereditary Phaeochromocytoma/Paraganglioma And Aortopathy In A Patient With Known Macroprolactinoma: A Series Of Incidental Findings

Abstract Disclosure: J.R. Kelly: None. S. Soule: None. P.J. Hunt: None. Background: The three P association (3PAs) describes the combination of pituitary adenoma and phaeochromocytoma/paraganglioma. Recent case series describe a range of underlying genetic causes, including SDH mutations. We describe a patient with a macroprolactinoma and their subsequent incidental diagnoses of phaeochromocytoma and paraganglioma, with a pathogenic SDHA mutation. Clinical Case: A 58-year-old man had previously received a combination of medical therapy with cabergoline and transsphenoidal debulking surgery for a histologically confirmed macroprolactinoma. Due to a small risk of valvulopathy associated with cumulative doses of cabergoline, screening echocardiogram was requested after seven years of treatment. This showed a calcified bicuspid aortic valve and severe dilatation of the ascending aorta at 58mm. Prior to surgical repair, CT aorta was requested, which showed an incidental left adrenal lesion. Formal adrenal imaging and functional assessment confirmed a 50mm phaeochromocytoma, with a right para-aortic paraganglioma subsequently revealed on Ga-68 DOTATATE-PET scan. He described symptoms of catecholamine excess, with episodic palpitations, chest pain, and increasing anxiety over the previous year, on a background of hypertension. Hereditary phaeochromocytoma/paraganglioma gene panel revealed a pathogenic mutation in SDHA (c.1663+1G&amp;gt;T) – a splicing variant, likely resulting in nonsense decay. Screening was recommended for his three children. He initiated alpha blockade with doxazosin, then beta blockade with metoprolol, prior to open adrenalectomy and excision of paraganglioma. Histology confirmed a left phaeochromocytoma (Ki67 0.1%, PASS score 8, no vascular or capsular invasion) and a paraganglioma. Post-operative plasma normetanephrine normalised (406 pmol/L, pre-operative 6776 pmol/L, normal &amp;lt;1200 pmol/L) and the patient described resolution of symptoms. He subsequently underwent tissue aortic valve replacement and Bentall’s procedure. Histology showed severe atherosclerosis with diffuse medial degeneration of the aorta. Repeat Ga-68 DOTATATE-PET seven months later showed no evidence of residual or recurrent disease. Ongoing management includes cabergoline, annual plasma metanephrine measurement, and intermittent MRI of pituitary and base of skull to coccyx. Conclusion: Macroprolactinomas are relatively common, with only a small proportion associated with underlying genetic abnormalities. This case describes a patient with 3PAs, initially presenting with a macroprolactinoma, with incidental detection of phaeochromocytoma and paraganglioma and subsequent identification of a pathogenic SDHA mutation. In the context of a calcified bicuspid aortic valve and severe aortic dilatation, pre-operative alpha blockade allowed successful surgical management of both potentially life-threatening conditions. Presentation: 6/3/2024

Unraveling aortic hemodynamics using fluid structure interaction: biomechanical insights into bicuspid aortic valve dynamics with multiple aortic lesions.

Aortic lesions, exemplified by bicuspid aortic valves (BAVs), can complicate congenital heart defects, particularly in Turner syndrome patients. The combination of BAV, dilated ascending aorta, and an elongated aortic arch presents complex hemodynamics, requiring detailed analysis for tailored treatment strategies. While current clinical decision-making relies on imaging modalities offering limited biomechanical insights, integrating high-performance computing and fluid-structure interaction algorithms with patient data enables comprehensive evaluation of diseased anatomy and planned intervention. In this study, a patient-specific workflow was utilized to biomechanically assess a Turner syndrome patient's BAV, dilated ascending aorta, and elongated arch. Results showed significant improvements in valve function (effective orifice area, EOA increased approximately twofold) and reduction in valve stress (~ 1.8-fold) following virtual commissurotomy, leading to enhanced flow dynamics and decreased viscous dissipation (~ twofold) particularly in the ascending aorta. However, increased viscous dissipation in the distal transverse aortic arch offset its local reduction in the AAo post-intervention, emphasizing the elongated arch's role in aortic hemodynamics. Our findings highlight the importance of comprehensive biomechanical evaluation and integrating patient-specific modeling with conventional imaging techniques for improved disease assessment, risk stratification, and treatment planning, ultimately enhancing patient outcomes.

Aortic root replacement for bicuspid aortic valve dysfunction does not impair survival rates

BackgroundPatients with a bicuspid aortic valve carry an increased risk for developing an ascending aortic aneurysm due to intrinsic aortic wall alterations. A lower threshold for aortic surgery may therefore be considered in these patients, especially in those who require aortic valve surgery. This study aimed to compare the outcomes of an isolated aortic valve replacement with that of an aortic root replacement in bicuspid aortic valve patients with an indication for aortic valve surgery.MethodsPatients were included in retrospect from a tertiary academic hospital. Included patients received an elective aortic valve (AVR) or a composite valve-graft conduit (both mechanical and biological) between 2006 and 2021 without any concomitant procedure. Mortality data were retrieved from a national database and comparisons, including survival analyses, were performed between both groups.ResultsA total of 132 isolated AVR and 149 aortic root replacements were included. Patients who received an isolated AVR were significantly older than the aortic root replacement group (62.9 vs. 57.7 year respectively, p < 0.001). Survival analyses showed a comparable long-term mortality between both groups (8.1% vs. 9.1%, p = 0.321).ConclusionThis study shows that performing an aortic root replacement with a composite valve-graft conduit in bicuspid aortic valve patients does not impair the survival outcomes. In the light of preventing potential future aortic complications within this patient group with a congenitally and structurally weakened aortic wall, a more aggressive approach towards the treatment of BAV aortopathy might be considered.

TCT-138 The Effect of Transcatheter Heart Valve Size and Deployment Height on Eccentricity in Bicuspid Aortic Valve: A Patient-Specific Simulation Study

TCT-138 The Effect of Transcatheter Heart Valve Size and Deployment Height on Eccentricity in Bicuspid Aortic Valve: A Patient-Specific Simulation Study

TCT-133 Volume Expansion Rate and Valve Dysfunction of Prosthesis in Patients With Bicuspid Aortic Valves and Small Aortic Annuli Who Underwent TAVR: Results From 240 Pre- and Post-TAVR Paired Computed Tomography Evaluation

TCT-133 Volume Expansion Rate and Valve Dysfunction of Prosthesis in Patients With Bicuspid Aortic Valves and Small Aortic Annuli Who Underwent TAVR: Results From 240 Pre- and Post-TAVR Paired Computed Tomography Evaluation

TCT-137 Outcomes of Patients With Bicuspid Aortic Valve Undergoing Transcatheter Aortic Valve Replacement Using the Navitor Self-Expanding Valve: Results From an International Multicenter Registry

TCT-137 Outcomes of Patients With Bicuspid Aortic Valve Undergoing Transcatheter Aortic Valve Replacement Using the Navitor Self-Expanding Valve: Results From an International Multicenter Registry

TAVR in tapered raphe-type stenotic bicuspid aortic valves: excellent results in challenging anatomies

TAVR in tapered raphe-type stenotic bicuspid aortic valves: excellent results in challenging anatomies

Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A Single-Center, Observational Study

Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1–43 BAV controls and group 2–30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation.

External fixation of an internal aortic annuloplasty device: advancing the technique.

We present a modified technique of Hemispherical Aortic Annuloplasty Reconstructive Technology (HAART) 200 annuloplasty ring implantation in bicuspid aortic valve morphology by external fixation of the looping sutures to avoid common complications associated with the original implantation technique. Preliminary results are promising and should be confirmed in subsequent multicentre studies.

Interrupted aortic arch with severe aortic stenosis in an adult bicuspid aortic valve patient

Interrupted aortic arch with severe aortic stenosis in an adult bicuspid aortic valve patient

CharActeristics, sizing anD outcomes of stenotic, tapered, rapHe-type bicuspid aOrtic valves treated with trans-catheter device implantation: Insights the AD HOC registry

BackgroundRaphe-type bicuspid aortic valve (BAV) is a potential hostile scenario in trans-catheter aortic valve replacement (TAVR) due to pronounced calcium burden, possibly associated with tapered valve configuration. Trans-Catheter heart valve (THV) sizing strategy (annular vs. supra-annular) is controversial in this valve subtype. ObjectivesTo describe the phenotypical characteristics of severe, tapered, raphe-type, BAV stenosis undergoing TAVR and to explore safety and efficacy of modern-generation THVs, analysing the impact of annular and supra-annular sizing strategies on short- and mid-terms outcomes. MethodsThis is a retrospective, multicenter registry enrolling consecutive stenotic Sievers type 1 BAV treated with TAVR. Study population was divided into tapered and non-tapered configuration according to MSCT analysis. Matched comparison between annular and supra-annular sizing groups was performed in tapered population. ResultsFrom January 2016 to June 2023, 897 patients were enrolled. Of them, 696 patients displayed a tapered configuration. Of those, 510 received a THV according to annular sizing. After propensity score matching 186 matched pairs were selected. Technical success (96.2 % vs 94.1 %, OR 1.61 [0.61–4.24], p = 0.34), 30-day device success (83.6 % in both groups, OR 1.42 [0.78–2.57], p = 0.25) and 30-day early safety (71.8 % vs 70.5 %, OR 1.07 [0.68–1.68], p = 0.78) were similar between the annular and supra-annular sizing groups; a higher post-TAVR gradient was observed in supra-annular group, although it was only 2 mmHg mean. At mid-term follow-up, the rate of clinical efficacy was 84.7 %. ConclusionsTAVR with modern-generation devices is safe and effective for tapered raphe-type BAV, showing comparable results for annular and supra-annular sizing strategies.

Inclusion body myositis coexisting with severe aortic stenosis due to bicuspid aortic valve: A case report and literature review of cardiac involvement in inclusion body myositis

AbstractInclusion body myositis (IBM) is an idiopathic inflammatory myopathy, but cardiac involvement has rarely been reported. Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, the relationship between IBM and valvular heart disease remains unknown. We herein report the first case of a 68‐year‐old male patient with IBM coexisting with severe aortic stenosis due to BAV that was successfully treated with aortic valve replacement. To date, only 10 cases of IBM with cardiac manifestation, including our case, have been reported, and we review the current literature on cardiac involvement in patients with IBM.

A case report of critical aortic stenosis diagnosed utilizing non-imaging continuous wave Doppler probe

Abstract Background Aortic stenosis (AS) is the most commonly acquired valvular pathology in the western world. Aortic stenosis severity is typically evaluated with Doppler echocardiography. Evaluation of aortic gradients using standard Doppler echocardiography from the apical window may underestimate the true gradient due to misalignment of blood flow to the ultrasound beam and is often better evaluated from other imaging windows using a non-imaging continuous wave Doppler (NI-CWD) probe. Herein, we describe a unique case of AS being underestimated by dynamic acoustic shadowing from the apical window rather than beam misalignment. Case summary The patient is a Hispanic 31-year-old male with a congenital bicuspid aortic valve who underwent a balloon aortic valvuloplasty at age 13. At age 31, the patient underwent a repeat transthoracic echocardiogram (TTE) that was largely unchanged from his prior TTE from 15 years prior. Notably on this TTE, there was acoustic shadowing of colour Doppler in the distal left ventricular outflow tract and aortic valve during systole. While gradients only suggested moderate AS, the degree of left ventricular hypertrophy was suspicious for more severe AS. Only by using the NI-CWD probe at the right sternal border were we able to identify very severe AS with a peak velocity of 6.5 m/s and a mean gradient of 100 mmHg. Discussion In our specific case, dynamic acoustic shadowing of the aortic valve from the apical window obscured both imaging and Doppler signals. This acoustic shadowing was not present from the right sternal border with the NI-CWD probe, leading to an over 100% increase in aortic valve peak velocity and proper correction of AS severity. This allowed for expedited care and underscores the importance of such techniques.

Transcatheter Aortic Valve Replacement is Ready for Most Low-risk Patients: A Systematic Review of the Literature.

Transcatheter aortic valve replacement (TAVR) has undergone rapid expansion, emerging as a viable therapeutic option for low-risk patients in lieu of surgical aortic valve replacement. This paper aims to provide a review of the scientific evidence concerning TAVR in low-risk patients, encompassing both observational and clinical trial data. Furthermore, a substantial proportion of low-risk patients possesses a bicuspid aortic valve, necessitating careful examination of the pertinent anatomic and clinical considerations to TAVR that is highlighted in this review. Additionally, the review expands upon some of the unique challenges associated with alternate access in low-risk patients evaluated for TAVR. Last, this review outlines the pivotal role of a multidisciplinary heart team approach in the execution of all TAVR procedures and the authors' vision of 'minimalist TAVR' as a new era in low-risk TAVR.

Flow quantification within the aortic ejection tract using 4D flow cardiac MRI in patients with bicuspid aortic valve: Implications for the assessment of aortic regurgitation

PurposeThe purpose of this study was to evaluate the performance of four-dimensional (4D) flow cardiac MRI in quantifying aortic flow in patients with bicuspid aortic valve (BAV). Materials and methodsPatients with BAV who underwent transthoracic echocardiography (TTE) and 4D flow cardiac MRI were prospectively included. Aortic flow was quantified using two-dimensional phase contrast velocimetry at the sinotubular junction and in the ascending aorta and using 4D flow in the regurgitant jet, in the left ventricular outflow tract, at the aortic annulus, the sinotubular junction, and the ascending aorta, with or without anatomical tracking. Flow quantification was compared with ventricular volumes, pulmonary flow using Pearson correlation test, bias and limits of agreement (LOA) using Bland Altman method, and with multiparametric transthoracic echocardiography quantification using weighted kappa test. ResultsEighty-eight patients (63 men, 25 women) with a mean age of 50.5 ± 14.8 (standard deviation) years (age range: 20.8–78.3) were included. Changes in flow with or without tracking were modest (< 5 mL). The best correlation was obtained at the aortic annulus for forward volume (r = 0.84; LOA [-28.4; 25.3] mL) and at the regurgitant jet and sinotubular junction for regurgitant volume (r = 0.68; LOA [-27.8; 33.8] and r = 0.69; LOA [-28.6; 24.2] mL). A combined approach for regurgitant fraction and net volume calculations using forward volume measured at ANN and regurgitant volume at sinotubular junction performed better than each level taken separately (r = 0.90; LOA [-20.7; 10.0] mL and r = 0.48, LOA [-33.8; 33.4] %). The agreement between transthoracic echocardiography and 4D flow cardiac MRI for aortic regurgitation grading was poor (kappa, 0.13 to 0.42). ConclusionIn patients with BAV, aortic flow quantification by 4D flow cardiac MRI is the most accurate at the annulus for the forward volume, and at the sinotubular junction or directly in the jet for the regurgitant volume.

Greater TIMP-1 protein levels and neointimal formation represent sex-dependent cellular events limiting aortic vessel expansion in female rats.

Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and neointimal growth secondary to a reduction of medial elastin content represent sex-dependent events limiting aortic vessel expansion in females. TIMP-1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP-2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2-treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re-entered the G2-M phase whereas VSMC cell cycle re-entry was attenuated in the CaCl2-treated infrarenal aorta of male rats. Thus, greater TIMP-1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2-treatment of the infrarenal aorta of female rats represents a sex-dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.

Effect of Sport Activity on Uncomplicated Bicuspid Aortic Valve: Long-Term Longitudinal Echocardiographic Study.

The bicuspid aortic valve (BAV) is a congenital heart defect that can lead to certain complications (aortic stenosis, regurgitation, dilatation and endocarditis), the diagnosis and clinical monitoring of which are effectively entrusted to transthoracic echocardiography (TTE). The impact of training on the natural history of the disease remains unclear. A retrospective cohort of athletes with uncomplicated BAV aged 18-50 years, who underwent at least 2 TTEs with a minimum follow-up of 5 years, subdivided according to the level of physical activity during follow-up into ''untrained'' and ''trained'', was collected. 47 athletes (87.3% male, median 21.0, (18.0; 33.0) years) were included. Median follow-up was 11.6 (8.4; 16.3) years. No statistically significant difference in the growing rate of aorta, left ventricle, nor a significant worsening of aortic stenosis and regurgitation was found. Moreover, there was no significant correlation between weekly training minutes during follow-up and the echocardiographic parameters related to heart size and function. In BAV without major complications, high training volumes do not correspond to a more rapid and significant deterioration in valve function nor to a more rapid increase in aortic or cardiac chamber size.