Calcified Bicuspid Aortic Valve Research Articles

Severe acute recoil following transcatheter aortic valve replacement with a self-expanding prosthesis in a heavily calcified bicuspid aortic valve.

Bicuspid aortic valve (BAV) is one of the most common congenital valvular heart diseases occurring in 0.5-2% of the general population, in 2-6% of patients with severe aortic stenosis (AS) and up to 20% of octo/nonagenarians undergoing surgery. In this regard, Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic alternative. At the present time, there is not enough evidence to determine which is the best therapeutic approach for AS in BAV. We report a severe acute recoil following TAVR with a self-expanding prosthesis in heavily calcified BAV. In addition, we provide an updated review of the clinical significance of prosthesis underexpansion in the medium-term.

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>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 <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

Spontaneous calcified cerebral emboli: a comprehensive review and proposed diagnostic criteria.

Spontaneous calcified cerebral emboli (SCCE) secondary to aortic valve calcification are a rare and underreported cause of acute ischaemic stroke. Only five cases of SCCE secondary to bicuspid aortic valve calcification have been reported in the literature. This review includes a unique case example of acute ischaemic stroke secondary to SCCE, as the first manifestation of a calcified bicuspid aortic valve. This is the first clinical case of calcified cerebral emboli (CCE) associated with borderzone infarction ('cortical ribbon sign'). Whilst previously assumed that most CCE are secondary to iatrogenic causes, recent literature suggests the majority of CCE are spontaneous and clinically silent. Despite CT imaging widely considered the 'gold standard' for diagnosis, CCE are frequently misdiagnosed and missed entirely. Misdiagnosis of CCE may have catastrophic consequences due to the high risk of recurrence and missed opportunity to prevent neurological disability and death. This review presents a revised CCE diagnostic criteria, using evidence that has emerged over the last decade to create both Compulsory (Major) and Supporting (Minor) criteria. Current CCE management is not evidence based and remains largely speculative. SCCE may be the first manifestation of cardiac or vascular disease and diagnosis should trigger aggressive treatment of emboligenic sources. Future epidemiological studies, analysing symptomatic and asymptomatic SCCE patients, would be beneficial in providing accurate quantification of disease burden. Other future research directions include exploring intracranial stenting for CCE revascularisation and cerebral intravascular lithotripsy.

889 ATRIOVENTRICULAR BLOCK, AN UNUSUAL CLINICAL PRESENTATION OF CALCIFIED BICUSPID AORTIC VALVE

Abstract Background Bicuspid aortic valve (BAV) is the most frequent congenital valve disease in adults. It is often associated with other congenital cardiac defects. Sometimes it is associated with aortic dilatation. BAV is an heterogeneous disease with varying valve morphology (asymmetrical cusp size and rafe), annulus geometry and size, asymmetrical calcification of the aortic valve and left ventricular outflow tract. Case Report A 32 year-old male patient was diagnosed with bicuspid aortic valve after several cardiologic visits for eligibility to competitive sport. Since April 2021 he developed a progressive exertional dyspnea for strenuous efforts. In February 2022, he was referred to our department after a Holter ECG showed a bradyarrhythmia with complete atrioventricular block. The echocardiography evaluation demonstrated a preserved ejection fraction and a bicuspid aortic valve with a mild-moderate regurgitation. The coronary computed tomography showed a thick and calcified bicuspid aortic valve with a coarse calcification of the anterior cuspid that involve the pars membranacea of the interventricular septum. The ergometric exercise demonstrated chronotropy incompetence. The tomography confirmed the mildy aortic root dilatation. Therefore, an MRI was performed and reported a small laminar LGE on the infero-lateral wall of the left ventricle, of unclear significance. He underwent Dual-Chamber permanent pacemaker implantation. A conservative approach was preferred over valvular replacement, considering the mild aortic root dilatation on a background of mild-to- moderate aortic insufficiency. Conclusion Our case is unusual given the bicuspid aortic valve concomitant with atrioventricular block, which was connected with the location of the calcification. Thus, the aim of our case report is, to describe a complication to this condition which, although rare, represents a different clinical presentation of the pathology itself in a young adult.

594 HIDDEN CAUSES FOR UNEXPLAINED SINCOPE

Abstract Bicuspid aortic valve (BAV) is a congenital cardiac abnormality, affecting approximately 1%-2% of the general population (male > female). A 33-year-old man was admitted to emergency department (ED) for syncope during exertion. He had a history of cigarette smoking with a known previously discovered BAV with mild stenosis. TTE showed a severely calcified bicuspid aortic valve with severe stenosis and regurgitation. ECGs showed frequent asymptomatic complete hearth block (CHB), unresponsive to isoprenaline infusion. He underwent ministernotomy aortic valve replacement (AVR) with mechanical valve. During hospital stay, the 24h ECG telemetric monitoring did not show any A-V disturbance and TTE demonstrated normal prosthesis function. Pacemaker implantation was delayed, Follow-up was performed at 1, 6 and 10 months after surgery: 24h-ECG recordings were performed showing no A-V conduction disturbances. At 1 year, during routine medical screening, cardiac frequency of 38 bpm was detected (ECG revealed sinus rhythm with CHB and junctional escape rhythm of 38 bpm). ICCU echocardiogram showed good ventricular and prosthesis function. Therefore, a dual-chamber MRI compatible pacemaker was implanted. Few cases are reported in literature of young patients presenting with A-V block having a severely calcified aortic bicuspid valve. Their management is poorly explored, and therapies (medical therapy, aortic valve replacement and pacemaker implantation) are not fully evidence based. In literature, 3 cases of possible reversibility of conducting system disorders after severe stenotic aortic valve surgery are described. Noninvasive strategy was initially successful as demonstrated by both the post-operative absence of any AV conduction disturbance and/or symptoms and the close follow-up monitoring. Despite of previous evidence, our experience demonstrates that a complete heart block can recur following aortic valve surgery, even in young patients. Initial presentation of CHB was intermittent, suggesting that the structural damage to the conducting system could not be irreversible; thus, it could positively respond to valve surgery. Unfortunately, in CHB with calcific aortic stenosis patients should be considered for PM implantation at the time of aortic surgery. When a waiting strategy prevails, especially for young patients, close monitoring and follow-up must be warranted to early detect A-V disturbances recurrence.

"Roof" technique-a modified aortotomy closure in Y-incision aortic root enlargement upsizing 3-4 valve sizes.

"Roof" technique-a modified aortotomy closure in Y-incision aortic root enlargement upsizing 3-4 valve sizes.

Transcription factor Sp2 promotes TGFB-mediated interstitial cell osteogenic differentiation in bicuspid aortic valves through a SMAD-dependent pathway

Calcification of the bicuspid aortic valve (BAV) involves differential expression of various RNA genes, which is achieved through complex regulatory networks that are controlled in part by transcription factors and microRNAs. We previously found that miR-195–5p regulates the osteogenic differentiation of valvular interstitial cells (VICs) by targeting the TGF-β pathway. However, the transcriptional regulation of miR-195–5p in calcified BAV patients is not yet clear. In this study, stenotic aortic valve tissues from patients with BAVs and tricuspid aortic valves (TAVs) were collected. Candidate transcription factors of miR-195–5p were predicted by bioinformatics analysis and tested in diseased valves and in male porcine VICs. SP2 gene expression and the corresponding protein levels in BAV were significantly lower than those in TAV, and a low SP2 expression level environment in VICs resulted in remarkable increases in RNA expression levels of RUNX2, BMP2, collagen 1, MMP2, and MMP9 and the corresponding proteins. ChIP assays revealed that SP2 directly bound to the transcription promoter region of miR-195–5p. Cotransfection of SP2 shRNA and a miR-195–5p mimic in porcine VICs demonstrated that SP2 repressed SMAD7 expression via miR-195–5p, while knockdown of SP2 increased the mRNA expression of SMAD7 and the corresponding protein and attenuated Smad 2/3 expression. Immunofluorescence staining of diseased valves confirmed that the functional proteins of osteogenesis differentiation, including RUNX2, BMP2, collagen 1, and osteocalcin, were overexpressed in BAVs. In Conclusion, the transcription factor Sp2 is expressed at low levels in VICs from BAV patients, which has a negative impact on miR-195–5p expression by binding its promoter region and partially promotes calcification through a SMAD-dependent pathway.

C10. An ultra-rare case of Hutchinson–Gilford progeria syndrome with severe aortic regurgitation due to bicuspid aortic valve in a 9-year-old girl

Abstract Background Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare autosomal dominant that result in progressive premature aging syndrome. Cardiovascular diseases become the main cause of mortality including myocardial infarction, interstitial myocardial fibrosis, hypertension and calcification of the mitral and aortic valves. However, the relationship between HGPS and bicuspid aortic valve (BAV) has not been documented yet. Case Summary A 9-year-old girl with HGPS presented to the outpatient clinic with a complaint of shortness of breath since 5 years ago, especially when she did moderate physical activity. Chest pain and palpitation were denied. Her physical examination revealed short stature, thin, wrinkled skin, craniofacial disproportion with alopecia, shrunken facies and prominent scalp veins. There was failure to thrive and diastolic murmur grade 2/4 is heard on the aortic area. Laboratory test showed leukocytosis. Transthoracic echocardiogram showed severe aortic regurgitation due to calcified bicuspid aortic valve and mild mitral regurgitation. She was managed by conservative therapy because her parents were still considering the aortic valve repair procedure. Discussion The HGPS patient with severe aortic regurgitation due to BAV should be managed to reduce cardiovascular complications. Aortic valve repair is an interesting alternative to replacement managing aortic regurgitation due to BAV in young adults. Recently, advanced science about BAV disease and refinement of surgical techniques improved standardization of BAV repair procedure.

C10. An ultra-rare case of Hutchinson–Gilford progeria syndrome with severe aortic regurgitation due to bicuspid aortic valve in a 9-year-old girl

Abstract Background Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare autosomal dominant that result in progressive premature aging syndrome. Cardiovascular diseases become the main cause of mortality including myocardial infarction, interstitial myocardial fibrosis, hypertension and calcification of the mitral and aortic valves. However, the relationship between HGPS and bicuspid aortic valve (BAV) has not been documented yet. Case Summary A 9-year-old girl with HGPS presented to the outpatient clinic with a complaint of shortness of breath since 5 years ago, especially when she did moderate physical activity. Chest pain and palpitation were denied. Her physical examination revealed short stature, thin, wrinkled skin, craniofacial disproportion with alopecia, shrunken facies and prominent scalp veins. There was failure to thrive and diastolic murmur grade 2/4 is heard on the aortic area. Laboratory test showed leukocytosis. Transthoracic echocardiogram showed severe aortic regurgitation due to calcified bicuspid aortic valve and mild mitral regurgitation. She was managed by conservative therapy because her parents were still considering the aortic valve repair procedure. Discussion The HGPS patient with severe aortic regurgitation due to BAV should be managed to reduce cardiovascular complications. Aortic valve repair is an interesting alternative to replacement managing aortic regurgitation due to BAV in young adults. Recently, advanced science about BAV disease and refinement of surgical techniques improved standardization of BAV repair procedure.

Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations.

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85ms-1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.

A rare cause of acute ST-elevation myocardial infarction: a case of coronary embolism secondary to calcified bicuspid aortic valve

Abstract Coronary embolism is an uncommon cause of acute myocardial infarction, which can have a similar clinical presentation to a plaque rupture event with acute onset of ischaemic symptoms, ST segment elevation on electrocardiogram (ECG) and significant elevation in cardiac troponin, requiring immediate intervention. We report the case of a middle-aged female with a background history of previous non-ST elevation myocardial infarction, bicuspid aortic valve with severe stenosis and metastatic breast cancer. The patient underwent emergency coronary angiography following acute onset central chest pain and evidence of anterior ST segment elevation on ambulance 12-lead ECG. The procedure revealed complete occlusion of the mid left anterior descending coronary artery with immediate flow restoration following embolus aspiration and subsequent normal appearance of the left anterior descending coronary artery. Gross examination of the aspirated specimen resembled a calcified hard lump, which was further confirmed on microscopic examination revealing calcified fibrous tissue most likely an embolus from the calcified bicuspid aortic valve. The patient had evidence of near transmural myocardial infarction in the distribution of the left anterior descending coronary on cardiac magnetic resonance imaging (MRI). She made full recovery and was discharged on short-term dual antiplatelet therapy followed by lifelong aspirin and further assessment for aortic stenosis management.

Four-Dimensional Echocardiography: Getting to the Root of the Matter

The aortic root is a complex 3-dimensional (3D) structure that has considerable structural heterogeneity, depending on whether the pathologic abnormality is ventricular, annular, valvular, or aortic. Our understanding of the 3D nature of the aortic root has been limited by available planar 2D imaging. With the advent of 4D echocardiographic (4DE) imaging, the true 3D shape and dynamic 3D changes to the root throughout the cardiac cycle can now be appreciated (Figure 1). Accounting for changes over the cardiac cycle may help improve our understanding of the pathologic changes to the aortic root in various disease states. Novel measurements derived from this methodology could potentially be used to trigger and assess the success of aortic root interventions. Dynamic Volumetric Assessment of the Aortic Root: The Influence of Bicuspid Aortic Valve CompetenceThe Annals of Thoracic SurgeryVol. 112Issue 4PreviewAortic root evaluation is conventionally based on 2-dimensional measurements at a single phase of the cardiac cycle. This work presents an image analysis method for assessing dynamic 3-dimensional changes in the aortic root of minimally calcified bicuspid aortic valves (BAVs) with and without moderate to severe aortic regurgitation. Full-Text PDF

Identification of a peripheral blood gene signature predicting aortic valve calcification.

Calcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational weeks 9, 13, and 22 and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at week 9 rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification.

Dynamic Volumetric Assessment of the Aortic Root: The Influence of Bicuspid Aortic Valve Competence

Aortic root evaluation is conventionally based on 2-dimensional measurements at a single phase of the cardiac cycle. This work presents an image analysis method for assessing dynamic 3-dimensional changes in the aortic root of minimally calcified bicuspid aortic valves (BAVs) with and without moderate to severe aortic regurgitation. The aortic root was segmented over the full cardiac cycle in 3-dimensional transesophageal echocardiographic images acquired from 19 patients with minimally calcified BAVs and from 16 patients with physiologically normal tricuspid aortic valves (TAVs). The size and dynamics of the aortic root were assessed using the following image-derived measurements: absolute mean root volume and mean area at the level of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction, as well as normalized root volume change and normalized area change of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction over the cardiac cycle. Normalized volume change over the cardiac cycle was significantly greater in BAV roots with moderate to severe regurgitation than in normal TAV roots and in BAV roots with no or mild regurgitation. Aortic root dynamics were most significantly different at the mid-level of the sinuses of Valsalva in BAVs with moderate to severe regurgitation than in competent TAVs and BAVs. Echocardiographic reconstruction of the aortic root demonstrates significant differences in dynamics of BAV roots with moderate to severe regurgitation relative to physiologically normal TAVs and competent BAVs. This finding may have implications for risk of future dilatation, dissection, or rupture, which warrant further investigation.

Upregulated microRNA‑330‑3p promotes calcification in the bicuspid aortic valve via targeting CREBBP

One key risk factor of aortic valve stenosis in clinical practice is bicuspid aortic valve (BAV). Increasing evidence indicates that numerous microRNAs (miRs/miRNAs) are involved in BAV calcification via their target genes. miR-330-3p was found to be involved in the deterioration of BAV calcification by miR profiling in human calcified BAV and tricuspid aortic valve (TAV) tissues in the present study and the underlying mechanism was investigated. RNA sequencing was performed on four BAV and four TAV tissues from patients with aortic stenosis before these leaflets were examined for the expression levels of miR-330-3p and CREB-binding protein (CREBBP) by reverse transcription-PCR. The alteration of functional factors associated with calcification was also assessed by Western blotting and immunohistochemistry in human aortic tissue samples. The putative target of miR-330-3p was detected by dual-luciferase assay in 293 cells. Furthermore, the influence of miR-330-3p expression on osteogenic progression was explored in cultured porcine valve interstitial cells (VICs). Rescue experiments of CRBBP were performed to confirm the influence of the miR-330-3p-CREBBP pathway in the calcification progress in porcine VICs. RNA sequencing indicated distinct expression of miR-330-3p in human BAV tissues compared with TAV, which was then confirmed by PCR. CREBBP expression levels in human BAV and TAV leaflets also demonstrated the opposite alterations. This negative correlation was then confirmed in cultured porcine VICs. Under an osteogenic environment, cellular calcification was promoted in miR-330-3p-overexpressed porcine VICs expressing higher bone morphogenetic protein 2, Runt-related transcription factor 2, matrix metalloproteinase (MMP)-2, MMP-9 and collagen I compared with controls. Rescue experiments further confirmed that miR-330-3p played its role via targeting CREBBP in porcine VICs. Collectively, miR-330-3p was upregulated in calcified BAV compared with TAV. The upregulation of miR-330-3p promotes the calcification progress partially via targeting CREBBP.

The role of stress concentration in calcified bicuspid aortic valve.

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in the aging population, and is now believed to be a slow, progressive, yet actively regulated process. The disease progression can be divided into two phases: initiation phase associated with lipid deposition and inflammation response, and the later propagation phase with active calcification growth. It has been hypothesized that elevated mechanical stress plays a major role in both phases of disease progression. In order to identify a direct link between leaflet stress and calcification development, we performed patient-specific finite-element (FE) analyses of six bicuspid aortic valves (BAV), where the leaflets, raphe and calcifications were all considered. The results showed that during the initiation phase, calcium buildup is likely to occur along the leaflet-root attachment curve (ATC), and the commissures, which are subject to the most drastic changes in stress during the cardiac cycle. During the propagation phase, the presence of calcification would lead to local stress concentration along its boundary, hence further calcification growth. Three patterns of calcification formation were identified on BAV leaflets: 'radial', which extended radially from ATC into the leaflet belly region; 'commissure to commissure', which extended circumferentially along the coaptation; and 'raphe', which located in the vicinity of the raphe. Furthermore, we found a strong correlation between regions with a high risk of calcium buildup and regions with elevated mechanical stress. The high-risk regions predicted at diastole on the non-calcified leaflet from FE models agreed reasonably well with the in vivo calcification locations, which indicates that patient-specific FE modelling could help us to evaluate the potential risk of calcification formation in the early stage of CAVD.

TAKING VIRUSES TO HEART: AN INTERESTING CASE OF COXSACKIE MYOCARDITIS

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Diagnosing the cause of heart failure in young, healthy adults can be challenging and often associated with high morbidity. Here, we present a case of heart failure associated with viral myocarditis in a patient with a bicuspid aortic valve. CASE PRESENTATION: A 28-year-old man with no medical history presented with epigastric pain, nausea, vomiting, chest pain, and chills. On initial evaluation, he was afebrile, with a blood pressure of 102/72 mmHg, and a heart rate of 127 bpm. A 2/6 mid-systolic murmur and 2/6 early diastolic murmur were heard without jugular venous distension. Otherwise, his exam was unrevealing. Labs were significant for elevated liver function tests (AST 372 U/L and ALT 422 U/L), elevated creatinine of 1.64 mg/dL (no baseline available), and an elevated white blood cell count of 14.7 K/uL. Abdominal computed topography was unremarkable. A transthoracic echocardiogram showed a dilated left ventricle with moderate to severe global hypokinesis with an ejection fraction of 30%. A large 2.8 cm x 1.0 cm mass on the aortic valve was seen causing aortic stenosis and moderate to severe aortic regurgitation, concerning for endocarditis. The patient was empirically initiated on gentamicin and vancomycin but clinically deteriorated into presumptively septic shock requiring supplemental oxygen, vasopressors, and continuous renal replacement therapy for renal failure. He was taken to the operating room for emergent resection and replacement of the aortic valve. However, intraoperatively the surgeon found and removed a heavily calcified bicuspid aortic valve. His blood cultures and microbiology of his valve revealed no infectious organisms; antibiotics were discontinued. Slowly he improved clinically. Without clear reason for his decompensation, a viral panel was obtained and returned positive for coxsackie B virus. DISCUSSION: In the United States, myocarditis is uncommon, impacting only one percent of the population. The Coxsackie viruses are the most common cause of infectious myocarditis, and predominantly affect men with the average age of onset being 42 years old. The cardiac manifestations of the virus typically occur two weeks after viral infection and are caused by direct cytopathic effects, pathologic immune responses, or autoimmunity triggered by the infection. Therapy with ribavirin has shown to reduce mortality in rodent models if initiated soon after inoculation which limits its applicability in human treatment. In this patient, his viral illness precipitated his acute clinical condition in the setting of a congenital bicuspid aortic valve with calcification, and he was treated with supportive therapy. CONCLUSIONS: This case highlights the importance of evaluating for viral myocarditis in young patients with acute heart failure and nonspecific symptoms and the need to remain vigilant for undiagnosed structural heart defects in otherwise healthy patients. Reference #1: Tam, Patricia E. "Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.” Viral immunology 19.2 (2006): 133-146. Reference #2: O.V. Blagova, O.V. Blagova, A.V. Nedostup, E.A. Kogan, V.P. Sedov, Y.U.V. Frolova, S.L. Dzemeshkevich, A.G. Kupryanova, V.A. Zaidenov, A.E. Donnikov; High prevalence of viral and immune myocarditis in patients with "idiopathic” and genetic dilated cardiomyopathy: biopsy proved diagnosis, European Heart Journal, Volume 34, Issue suppl_1, 1 August 2013, P4238, https://doi.org/10.1093/eurheartj/eht309.P4238 DISCLOSURES: No relevant relationships by Kara Calhoun, source=Web Response No relevant relationships by Jennifer Duke, source=Web Response No relevant relationships by Brandy McKelvy, source=Web Response No relevant relationships by Abin Puravath, source=Web Response

Biomechanical modeling of transcatheter aortic valve replacement in a stenotic bicuspid aortic valve: deployments and paravalvular leakage.

Calcific aortic valve disease (CAVD) is characterized by stiffened aortic valve leaflets. Bicuspid aortic valve (BAV) is the most common congenital heart disease. Transcatheter aortic valve replacement (TAVR) is a treatment approach for CAVD where a stent with mounted bioprosthetic valve is deployed on the stenotic valve. Performing TAVR in calcified BAV patients may be associated with post-procedural complications due to the BAV asymmetrical structure. This study aims to develop refined computational models simulating the deployments of Evolut R and PRO TAVR devices in a representative calcified BAV. The paravalvular leakage (PVL) was also calculated by computational fluid dynamics simulations. Computed tomography scan of severely stenotic BAV patient was acquired. The 3D calcium deposits were generated and embedded inside a parametric model of the BAV. Deployments of the Evolut R and PRO inside the calcified BAV were simulated in five bioprosthesis leaflet orientations. The hypothesis of asymmetric and elliptic stent deployment was confirmed. Positioning the bioprosthesis commissures aligned with the native commissures yielded the lowest PVL (15.7 vs. 29.5mL/beat). The Evolut PRO reduced the PVL in half compared with the Evolut R (15.7 vs. 28.7mL/beat). The proposed biomechanical computational model could optimize future TAVR treatment in BAV patients. Graphical abstract.

Echocardiographic manifestations and chemical composition of stenotic bicuspid aortic valves.

Bicuspid aortic valve (BAV) is an inherited form of heart disease with only two aortic valve leaflets via a disorder of cardiac valvulogenesis. We investigated the in vivo echocardiographic features of cardiac morphology in patients with BAV and the ex vivo compositional components of all the excised BAV leaflets isolated from BAV patients. Three BAV patients were randomly selected. All patients underwent 2D transthoracic echocardiography (TTE) with a Doppler ultrasound tool. The compositional components of each respective BAV leaflet for all the excised BAVs were determined by a portable fiber-optic Raman spectroscopy. Preoperative TTE revealed the thickened and calcified BAV leaflets, and stenotic aortic flow for all BAV patients. These BAV patients exhibited severe aortic stenosis (AS) by the lower values of aortic valve area (AVA) index. One patient showed a more significant left ventricle hypertrophy, whereas two patients exhibited a significant aortic regurgitation (AR). In addition, three different Raman spectral patterns were summed up from 121 randomized Raman determinations for all the excised BAV leaflets. The main calcified deposition in each BAV leaflet was formed by large amounts of calcium hydroxyapatite and type-B carbonate apatite (Raman bands at 960 and 1070 cm-1). The calcified BAV leaflets were composed of different compositional components such as calcium hydroxyapatite, type-B carbonate apatite, lipids, proteins, cholesterol and β-carotene. The rare NL subtype of type 1 BAV morphotype was found in one patient, but two patients had the purely BAV morphotype with two equal-sized leaflets.

Different Notch signaling in cells from calcified bicuspid and tricuspid aortic valves

AimsCalcific aortic valve disease is the most common heart valve disease in the Western world. Bicuspid and tricuspid aortic valve calcifications are traditionally considered together although the dynamics of the disease progression is different between the two groups of patients. Notch signaling is critical for bicuspid valve development and NOTCH1 mutations are associated with bicuspid valve and calcification. We hypothesized that Notch-dependent mechanisms of valve mineralization might be different in the two groups. Methods and resultsWe used aortic valve interstitial cells and valve endothelial cells from patients with calcific aortic stenosis with bicuspid or tricuspid aortic valve. Expression of Notch-related genes in valve interstitial cells by qPCR was different between bicuspid and tricuspid groups. Discriminant analysis of gene expression pattern in the interstitial cells revealed that the cells from calcified bicuspid valves formed a separate group from calcified tricuspid and control cells. Interstitial cells from bicuspid calcified valves demonstrated significantly higher sensitivity to stimuli at early stages of induced proosteogenic differentiation and were significantly more sensitive to the activation of proosteogenic OPN, ALP and POSTIN expression by Notch activation. Notch-activated endothelial-to-mesenchymal transition and the corresponding expression of HEY1 and SLUG were also more prominent in bicuspid valve derived endothelial cells compared to the cells from calcified tricuspid and healthy valves. ConclusionEarly signaling events including Notch-dependent mechanisms that are responsible for the initiation of aortic valve calcification are different between the patients with bicuspid and tricuspid aortic valves.