Current state of the art in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures.

Atherogenic potential of microgravity hemodynamics in the carotid bifurcation: a numerical investigation.

Long-duration spaceflight poses multiple hazards to human health, including physiological changes associated with microgravity. The hemodynamic adaptations occurring upon entry into weightlessness have been associated with retrograde stagnant flow conditions and thromboembolic events in the venous vasculature but the impact of microgravity on cerebral arterial hemodynamics and function remains poorly understood. The objective of this study was to quantify the effects of microgravity on hemodynamics and wall shear stress (WSS) characteristics in 16 carotid bifurcation geometries reconstructed from ultrasonography images using computational fluid dynamics modeling.

Significance of aortoseptal angle anomalies to left ventricular hemodynamics and subaortic stenosis: A numerical study.

Purpose: Discrete subaortic stenosis (DSS) is an obstructive cardiac disease caused by a membranous lesion in the left ventricular (LV) outflow tract (LVOT). Although its etiology is unknown, the higher prevalence of DSS in LVOT anatomies featuring a steep aortoseptal angle (AoSA) suggests a potential role for hemodynamics. Therefore, the objective of this study was to quantify the impact of AoSA steepening on the LV three-dimensional (3D) hemodynamic stress environment.

Computational Assessment of Valvular Dysfunction in Discrete Subaortic Stenosis: A Parametric Study.

Purpose: Discrete subaortic stenosis (DSS) is a left-ventricular outflow tract (LVOT) obstruction caused by a membranous lesion. DSS is associated with steep aortoseptal angles (AoSAs) and is a risk factor for aortic regurgitation (AR). However, the etiology of AR secondary to DSS remains unknown.

Impact of Aortoseptal Angle Abnormalities and Discrete Subaortic Stenosis on Left-Ventricular Outflow Tract Hemodynamics: Preliminary Computational Assessment.

Discrete subaortic stenosis (DSS) is an obstruction of the left ventricular outflow tract (LVOT) due to the formation of a fibromuscular membrane upstream of the aortic valve. DSS is a major risk factor for aortic regurgitation (AR), which often persists after surgical resection of the membrane. While the etiology of DSS and secondary AR is largely unknown, the frequent association between DSS and aortoseptal angle (AoSA) abnormalities has supported the emergence of a mechanobiological pathway by which hemodynamic stress alterations on the septal wall could trigger a biological cascade leading to fibrosis and membrane formation.

Design and Computational Validation of a Novel Bioreactor for Conditioning Vascular Tissue to Time-Varying Multidirectional Fluid Shear Stress.

Purpose: The cardiovascular endothelium experiences pulsatile and multidirectional fluid wall shear stress (WSS). While the effects of non-physiologic WSS magnitude and pulsatility on cardiovascular function have been studied extensively, the impact of directional abnormalities remains unknown due to the challenge to replicate this characteristic in vitro. To address this gap, this study aimed at designing a bioreactor capable of subjecting cardiovascular tissue to time-varying WSS magnitude and directionality.

Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease.

Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue, causing an increased pressure gradient in the left ventricular outflow tract (LVOT). While surgical resection of the membrane has shown some success in eliminating the obstruction, it poses significant risks associated with anesthesia, sternotomy, and heart bypass, and it remains associated with a high rate of recurrence. Although a genetic etiology had been initially proposed, the association between DSS and left ventricle (LV) geometrical abnormalities has provided more support to a hemodynamic etiology by which congenital or post-surgical LVOT geometric derangements could generate abnormal shear forces on the septal wall, triggering in turn a fibrotic response.

Effect of arteriovenous graft flow rate on vascular access hemodynamics in a novel modular anastomotic valve device.

Purpose: Perturbed vascular access hemodynamics is considered a potential driver of intimal hyperplasia, the leading cause of vascular access failure. To improve vascular access patency, a modular anastomotic valve device has been designed to normalize venous flow between hemodialysis periods while providing normal vascular access during hemodialysis. The objective of this study was to quantify the effects of arteriovenous graft flow rate on modular anastomotic valve device vascular access hemodynamics under realistic hemodialysis conditions.

Wall Shear Stress Directional Abnormalities in BAV Aortas: Toward a New Hemodynamic Predictor of Aortopathy?

The bicuspid aortic valve (BAV) generates wall shear stress (WSS) abnormalities in the ascending aorta (AA) that may be responsible for the high prevalence of aortopathy in BAV patients. While previous studies have analyzed the magnitude and oscillatory characteristics of the total or streamwise WSS in BAV AAs, the assessment of the circumferential component is lacking despite its expected significance in this highly helical flow environment. This gap may have hampered the identification of a robust hemodynamic predictor of BAV aortopathy.

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study.

The bicuspid aortic valve (BAV) is a major risk factor for secondary aortopathy such as aortic dilation. The heterogeneous BAV morphotypes [left-right-coronary cusp fusion (LR), right-non-coronary cusp fusion (RN), and left-non-coronary cusp fusion (LN)] are associated with different dilation patterns, suggesting a role for hemodynamics in BAV aortopathogenesis. However, assessment of this theory is still hampered by the limited knowledge of the hemodynamic abnormalities generated by the distinct BAV morphotypes.

Simulations of morphotype-dependent hemodynamics in non-dilated bicuspid aortic valve aortas.

Bicuspid aortic valves (BAVs) generate flow abnormalities that may promote aortopathy. While positive helix fraction (PHF) index, flow angle (θ), flow displacement (d) and wall shear stress (WSS) exhibit abnormalities in dilated BAV aortas, it is unclear whether those anomalies stem from the abnormal valve anatomy or the dilated aorta. Therefore, the objective of this study was to quantify the early impact of different BAV morphotypes on aorta hemodynamics prior to dilation.

Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity.

Aim: To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects.

Methods: Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor.

Generation of Simulated Calcific Lesions in Valve Leaflets for Flow Studies.

Background And Aim Of The Study: Calcific aortic valve disease (CAVD) is the most common valvular disorder. While fluid stresses are presumed to play a role in disease progression, the valvular hemodynamic changes experienced over the course of CAVD remain largely unknown. The study aim was to develop a laboratory protocol for the fabrication of tissue valve models mimicking mild and moderate calcific stenosis, for future use in flow studies.

Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses.

Aim: To explore ex vivo the role of bone morphogenetic protein-4 (BMP-4) and transforming growth factor-beta1 (TGF-β1) in acute valvular response to fluid shear stress (FSS) abnormalities.

Methods: Porcine valve leaflets were subjected ex vivo to physiologic FSS, supra-physiologic FSS magnitude at normal frequency and supra-physiologic FSS frequency at normal magnitude for 48 h in a double-sided cone-and-plate bioreactor filled with standard culture medium. The role of BMP-4 and TGF-β1 in the valvular response was investigated by promoting or inhibiting the downstream action of those cytokines via culture medium supplementation with BMP-4 or the BMP antagonist noggin, and TGF-β1 or the TGF-β1 inhibitor SB-431542, respectively.

Etiology of bicuspid aortic valve disease: Focus on hemodynamics.

The bicuspid aortic valve (BAV) is the most common form of inheritable cardiac defect. Although this abnormality may still achieve normal valvular function, it is often associated with secondary valvular and aortic complications such as calcific aortic valve disease and aortic dilation. The clinical significance and economic burden of BAV disease justify the need for improved clinical guidelines and more robust therapeutic modalities, which address the root-cause of those pathologies.

Novel modular anastomotic valve device for hemodialysis vascular access: preliminary computational hemodynamic assessment.

Purpose: Arteriovenous graft patency is limited by terminal occlusion caused by intimal hyperplasia (IH). Motivated by evidence that flow disturbances promote IH progression, a modular anastomotic valve device (MAVD) was designed to isolate the graft from the circulation between dialysis periods (closed position) and enable vascular access during dialysis (open position). The objective of this study was to perform a preliminary computational assessment of the device ability to normalize venous flow between dialysis periods and potentially limit IH development and thrombogenesis.

Bicuspid aortic valve hemodynamics induces abnormal medial remodeling in the convexity of porcine ascending aortas.

The type-I bicuspid aortic valve (BAV), which differs from the normal tricuspid aortic valve (TAV) most commonly by left-right coronary cusp fusion, is frequently associated with secondary aortopathies. While BAV aortic dilation has been linked to a genetic predisposition, hemodynamics has emerged as a potential alternate etiology. However, the link between BAV hemodynamics and aortic medial degeneration has not been established.

Steady flow hemodynamic and energy loss measurements in normal and simulated calcified tricuspid and bicuspid aortic valves.

The bicuspid aortic valve (BAV), which forms with two leaflets instead of three as in the normal tricuspid aortic valve (TAV), is associated with a spectrum of secondary valvulopathies and aortopathies potentially triggered by hemodynamic abnormalities. While studies have demonstrated an intrinsic degree of stenosis and the existence of a skewed orifice jet in the BAV, the impact of those abnormalities on BAV hemodynamic performance and energy loss has not been examined. This steady-flow study presents the comparative in vitro assessment of the flow field and energy loss in a TAV and type-I BAV under normal and simulated calcified states.

Defining the role of fluid shear stress in the expression of early signaling markers for calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between cardiovascular risk factors, molecular signaling networks and hemodynamic cues. While earlier studies demonstrated that alterations in fluid shear stress (FSS) on the fibrosa could trigger inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. This knowledge could be critical to the elucidation of key CAVD risk factors such as congenital valve defects, aging and hypertension, which are known to generate FSS disturbances.

Ex vivo evidence for the contribution of hemodynamic shear stress abnormalities to the early pathogenesis of calcific bicuspid aortic valve disease.

The bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and is frequently associated with calcific aortic valve disease (CAVD). The most prevalent type-I morphology, which results from left-/right-coronary cusp fusion, generates different hemodynamics than a tricuspid aortic valve (TAV). While valvular calcification has been linked to genetic and atherogenic predispositions, hemodynamic abnormalities are increasingly pointed as potential pathogenic contributors.

Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease.

The bicuspid aortic valve (BAV) is associated with a high prevalence of calcific aortic valve disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD.

Hemodynamics and mechanobiology of aortic valve inflammation and calcification.

Cardiac valves function in a mechanically complex environment, opening and closing close to a billion times during the average human lifetime, experiencing transvalvular pressures and pulsatile and oscillatory shear stresses, as well as bending and axial stress. Although valves were originally thought to be passive pieces of tissue, recent evidence points to an intimate interplay between the hemodynamic environment and biological response of the valve. Several decades of study have been devoted to understanding these varied mechanical stimuli and how they might induce valve pathology.