UNASSIGNED: Primary pulmonary vein stenosis (PVS) is a rare congenital heart disease that proves to be a clinical challenge due to the rapidly progressive disease course and high rates of treatment complications. PVS intervention is frequently faced with in-stent restenosis and persistent disease progression despite initial venous recanalization with balloon angioplasty or stenting. Alterations in wall shear stress (WSS) have been previously associated with neointimal hyperplasia and venous stenosis underlying PVS progression. Thus, the development of patient-specific three-dimensional (3D) in vitro models is needed to further investigate the biomechanical outcomes of endovascular and surgical interventions.
UNASSIGNED: In this study, deidentified computed tomography images from three patients were segmented to generate perfusable phantom models of pulmonary veins before and after catheterization. These 3D reconstructions were 3D printed using a clear resin ink and used in a benchtop experimental setup. Computational fluid dynamic (CFD) analysis was performed on models in silico utilizing Doppler echocardiography data to represent the in vivo flow conditions at the inlets. Particle image velocimetry was conducted using the benchtop perfusion setup to analyze WSS and velocity profiles and the results were compared with those predicted by the CFD model.
UNASSIGNED: Our findings indicated areas of undesirable alterations in WSS before and after catheterization, in comparison with the published baseline levels in the healthy in vivo tissues that may lead to regional disease progression.
UNASSIGNED: The established patient-specific 3D in vitro models and the developed in vitro-in silico platform demonstrate great promise to refine interventional approaches and mitigate complications in treating patients with primary PVS.

Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration from cranial venous plexus to form CoW arteries. Subsequently, acta2+ VSMCs differentiate from pdgfrb+ mural cell progenitors after they were recruited to CoW arteries. The progression of VSMC differentiation exhibits a spatiotemporal pattern, advancing from anterior to posterior CoW arteries. Analysis of blood flow suggests that earlier VSMC differentiation in anterior CoW arteries correlates with higher red blood cell velocity and wall shear stress. Furthermore, pulsatile flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is required for VSMC differentiation on zebrafish CoW arteries. Consistently, flow-responsive transcription factor klf2a is activated in ECs of CoW arteries prior to VSMC differentiation, and klf2a knockdown delays VSMC differentiation on anterior CoW arteries. In summary, our findings highlight blood flow activation of endothelial klf2a as a mechanism regulating initial VSMC differentiation on vertebrate brain arteries.

UNASSIGNED: Superior cavopulmonary connection (SCPC) for stage II palliation of hypoplastic left heart syndrome (HLHS) is achieved most frequently by either a bidirectional Glenn (BDG) or hemi-Fontan (HF) operation. The comparison of flow hemodynamic efficiency at the region of surgical reconstruction and in proximal pulmonary arteries has been evaluated primarily using computational modeling techniques with conflicting reports. The purpose of this descriptive study was to compare flow hemodynamics following stage II (BDG vs HF) using 4-dimensional flow magnetic resonance imaging (4D-Flow MRI) with particular focus on flow-mediated viscous energy loss (EL\') under matched hemodynamic conditions.
UNASSIGNED: Patients with hypoplastic left heart syndrome (HLHS) who underwent either HF or BDG as part of stage II palliation underwent pre-Fontan 4D-Flow MRI. Patients were matched by the pulmonary vascular resistance index, net superior vena cava (SVC) flow, right pulmonary artery (RPA) and left pulmonary artery (LPA) size, and age. Maximum EL\' throughout the cardiac cycle was calculated along the SVC-RPA and SVC-LPA tracts.
UNASSIGNED: Eight patients who underwent HF as part of their stage II single ventricle palliation were matched with 8 patients who underwent BDG. There were no differences between the 2 groups in median volumetric indices, including end-diastolic volume (P = .278) and end-systolic volume (P = .213). Moreover, no differences were observed in ejection fraction (P = .091) and cardiac index (P = .324). There also were no differences in peak EL\' measured along the SVC-RPA tract (median, 0.05 mW for HF vs 0.04 mW for BDG; P = .365) or along the SVC-LPA tract (median, 0.05 mW vs 0.04 mW; P = .741).
UNASSIGNED: The second stage of surgical palliation of HLHS using either HF or BDG results in similar flow-mediated viscous energy loss throughout the SCPC junction. 4D-Flow MRI and computational methods should be applied together to investigate flow hemodynamic patterns throughout the Fontan palliation and overall efficiency of the Fontan circuit.

OBJECTIVE: Flow through the proximal pulmonary arteries (PAs) of patients with repaired Tetralogy of Fallot (TOF) is known to be highly disordered and associated with significant regurgitation. The purpose of this study was to evaluate 4D-Flow MRI-derived viscous energy loss [Formula: see text])-as a result of non-efficient flow propagation, and relate this parameter to standard right ventricular (RV) size and function markers in patients with repaired TOF.
METHODS: Thirty-five patients with TOF and 14 controls underwent comprehensive 4D-Flow MRI evaluation for qualitative flow analysis and to calculate [Formula: see text] in the main and right pulmonary arteries. Sampled [Formula: see text] indices were correlated with the MRI-derived RV size and functional indices.
RESULTS: All patients with TOF exhibited abnormal, supra-physiologic helical/vortical formations in the PAs. Patients with TOF had significantly increased peak systolic [Formula: see text] (8.0 vs 0.5 mW, p < 0.001), time-averaged [Formula: see text] (2.5 vs. 0.2 mW, p < 0.001), and peak systolic [Formula: see text] indexed to stroke volume (0.082 vs. 0.012 mW/mL, p < 0.001). [Formula: see text] indexed to stroke volume correlated with the RV end-diastolic volume (R = 0.68, p < 0.001), end-systolic volume (R = 0.62, p < 0.001), ejection fraction (R = -0.45, p = 0.002), and cardiac index (R = 0.45, p = 0.002). The mean estimated energy loss due to [Formula: see text] with regard to input RV mechanical power was 4.7%.
CONCLUSIONS: This study demonstrates that patients with repaired TOF have highly abnormal flow conduction through the PAs which result into extensive viscous energy loss. This significant flow-mediated energy loss is associated with the RV volume and function, and might represent considerable loss of mechanical power generated by each cardiac cycle. Future studies are required to assess whether the abnormal flow conduction adds to the RV afterload and remodeling.
CONCLUSIONS: • Abnormal flow patterns through proximal pulmonary arteries in patients with TOF are associated with excessive viscous energy loss. • Inefficient flow conduction is associated with the RV dilation and reduced function and might contribute to the RV adaptive remodeling.

The maturation and long-term patency of transposed brachio-basilic arteriovenous fistulae can best be achieved not by adopting a two-stage construction procedure, but by using a loop configuration and an anastomosis angle that allows for the most favorable flow dynamics.

BACKGROUND: Left ventricular intracavitary flow (LVICF) characteristics reflect diastolic function. Right ventricular (RV) volume overload due to pulmonary regurgitation (PR) adversely impacts interventricular interactions and left ventricular (LV) function. This aimed to determine whether patients with PR and mild to moderate RV dilation after repair of tetralogy of Fallot (TOF) repair have abnormal LVICF, and to determine whether RV dilation and biventricular function correlate with LVICF abnormalities.
METHODS: Patients with repaired TOF with PR (n = 11) and controls (n = 11) underwent LVICF analysis. LV end-diastolic volume was partitioned into 4 flow components: direct flow, retained inflow, delayed ejection flow, and residual volume. Flow components were correlated with indexed biventricular size, function, and LV strain.
RESULTS: The TOF patients had reduced direct flow (35% vs 25%; P = .004) and increased residual volume (15% vs 24%; P = .026) compared with controls. Retained inflow and delayed ejection flow did not differ. Reduced direct flow correlated with increased RV end-diastolic volume index (R = 0.44; P = .042), RV end-systolic volume index (R = -0.46; P = .032), reduced RV ejection fraction (R = 0.45; P = .036), and reduced LV circumferential strain (R = 0.52; P = .014). Increased residual volume correlated with increased RV end-systolic volume index (R = 0.52; P = .013), reduced LV ejection fraction (R = -0.54; P = .010), and reduced LV circumferential strain (R = -0.44; P = .040).
CONCLUSIONS: Patients with repaired TOF with mild to moderate RV dilation have abnormal LV diastolic direct flow and increased recirculating residual volume. These changes correlate with the degree of RV dilation and impaired LV function.

The need to simulate the normal operating conditions of the human body is the key factor in every study and engineering process of bioelectronic devices designed for implantation. The Fontan procedure is an example of such a process aimed to support the human body function. It is a standard treatment method for patients with a functionally univentricular heart. However, it has significant drawbacks such as overload of the only functional heart ventricle that often leads to the necessity of the heart transplantation. In this study, we analyze the total cavopulmonary connection (TCPC) influence on the blood with and without connected auxiliary blood circulation pump. We investigate four different types of TCPC configurations, analyze blood pressure and different flow rate, study the turbulent kinetic energy distribution, and evaluate hydraulic and power losses for various cases. Finally, we calculate volumetric scalar shear stresses distribution and demonstrate the high potential of TCPC configuration with connected rotary pump as a tool for the load redistribution in the functional heart ventricle. This work is particularly relevant for improving existing TCPCs\' quality that can extend the life of Fontan patients. Moreover, it also applies to the reduction of morbidity and mortality of the patients waiting for the heart transplantation.

Patients with tetralogy of Fallot are at risk for late aortic complications due to progressive aortic root dilation and decreased aortic compliance. Early repair normalizes aortic dimensions by preadolescence. It is not known if early repair normalizes aortic wall histology and compliance or reduces late aortic complications. We used 4-dimensional flow magnetic resonance imaging to determine if children with tetralogy of Fallot repaired in infancy had normal aortic dimensions and to characterize the aortic wall hemodynamic state and luminal flow parameters in these patients.
Comprehensive aortic analysis with 4-dimensional flow magnetic resonance imaging was performed in 18 patients with tetralogy of Fallot who were repaired in infancy and compared with 18 normal volunteers. Peak systolic and time-averaged wall shear stress, relative area change, and distensibility were evaluated in standardized aortic planes. Qualitative grade scale flow analysis with interactive pathline visualization was used to detect pathologic flow patterns.
Thoracic aortic dimensions did not differ between groups, and all tetralogy of Fallot aortas were in normal range. In the tetralogy of Fallot group, ascending and descending aortic relative area change and distensibility were significantly reduced, and both peak systolic and time-averaged wall shear stress were elevated throughout the aorta. Supra-physiologic systolic helical formations occurred in the ascending aorta of 14 patients with tetralogy of Fallot (78%) versus 0 controls.
Despite early repair and normal aortic dimensions, preadolescents and adolescents with tetralogy of Fallot had elevated wall shear stress, increased stiffness, and pathologic systolic flow formations in the proximal aorta. Although early repair normalizes aortic dimensions in childhood, our findings suggest that patients with tetralogy of Fallot remain at risk for late aortic complications.