Machine learning detection of obstructive hypertrophic cardiomyopathy using a wearable biosensor.

Hypertrophic cardiomyopathy (HCM) is a heritable disease of heart muscle that increases the risk for heart failure, stroke, and sudden death, even in asymptomatic patients. With only 10-20% of affected people currently diagnosed, there is an unmet need for an effective screening tool outside of the clinical setting. Photoplethysmography uses a noninvasive optical sensor incorporated in commercial smart watches to detect blood volume changes at the skin surface. In this study, we obtained photoplethysmography recordings and echocardiograms from 19 HCM patients with left ventricular outflow tract obstruction (oHCM) and a control cohort of 64 healthy volunteers. Automated analysis showed a significant difference in oHCM patients for 38/42 morphometric pulse wave features, including measures of systolic ejection time, rate of rise during systole, and respiratory variation. We developed a machine learning classifier that achieved a C-statistic for oHCM detection of 0.99 (95% CI: 0.99-1.0). With further development, this approach could provide a noninvasive and widely available screening tool for obstructive HCM.

Thrust and Hydrodynamic Efficiency of the Bundled Flagella.

The motility mechanism of prokaryotic organisms has inspired many untethered microswimmers that could potentially perform minimally invasive medical procedures in stagnant fluid regions inside the human body. Some of these microswimmers are inspired by bacteria with single or multiple helical flagella to propel efficiently and fast. For multiple flagella configurations, the direct measurement of thrust and hydrodynamic propulsion efficiency has been challenging due to the ambiguous mechanical coupling between the flow field and mechanical power input. To address this challenge and to compare alternative micropropulsion designs, a methodology based on volumetric velocity field acquisition is developed to acquire the key propulsive performance parameters from scaled-up swimmer prototypes. A digital particle image velocimetry (PIV) analysis protocol was implemented and experiments were conducted with the aid of computational fluid dynamics (CFD). First, this methodology was validated using a rotating single-flagellum similitude model. In addition to the standard PIV error assessment, validation studies included 2D vs. 3D PIV, axial vs. lateral PIV and simultaneously acquired direct thrust force measurement comparisons. Compatible with typical micropropulsion flow regimes, experiments were conducted both for very low and higher Reynolds (Re) number regimes (up to a Re number = 0.01) than that are reported in the literature. Finally, multiple flagella bundling configurations at 0°, 90° and 180° helical phase-shift angles were studied using scaled-up multiple concentric flagella thrust elements. Thrust generation was found to be maximal for the in-phase (0°) bundling configuration but with ~50% lower hydrodynamic efficiency than the single flagellum. The proposed measurement protocol and static thrust test-bench can be used for bio-inspired microscale propulsion methods, where direct thrust and efficiency measurement are required.

Design Rationale and Performance Evaluation of the Wavelet Health Wristband: Benchtop Validation of a Wrist-Worn Physiological Signal Recorder.

BACKGROUND: Wearable and connected health devices along with the recent advances in mobile and cloud computing provide a continuous, convenient-to-patient, and scalable way to collect personal health data remotely. The Wavelet Health platform and the Wavelet wristband have been developed to capture multiple physiological signals and to derive biometrics from these signals, including resting heart rate (HR), heart rate variability (HRV), and respiration rate (RR). OBJECTIVE: This study aimed to evaluate the accuracy of the biometric estimates and signal quality of the wristband. METHODS: Measurements collected from 35 subjects using the Wavelet wristband were compared with simultaneously recorded electrocardiogram and spirometry measurements. RESULTS: The HR, HRV SD of normal-to-normal intervals, HRV root mean square of successive differences, and RR estimates matched within 0.7 beats per minute (SD 0.9), 7 milliseconds (SD 10), 11 milliseconds (SD 12), and 1 breaths per minute (SD 1) mean absolute deviation of the reference measurements, respectively. The quality of the raw plethysmography signal collected by the wristband, as determined by the harmonic-to-noise ratio, was comparable with that obtained from measurements from a finger-clip plethysmography device. CONCLUSIONS: The accuracy of the biometric estimates and high signal quality indicate that the wristband photoplethysmography device is suitable for performing pulse wave analysis and measuring vital signs.

Novel Cardiac Coordinate Modeling System for Three-Dimensional Quantification of Inflow Cannula Malposition of HeartMate II LVADs.

Optimal function of left ventricular assist devices (LVADs) depends on proper alignment of the inflow cannula (IC). Quantitative guidelines for IC angulation are lacking because of variation in cardiac geometry and difficulty in analyzing three-dimensional (3D) cannula orientation relative to the left ventricle (LV). Based on contrast-enhanced computed tomography images from five normal and five clinically malpositioned IC cases in patients with HeartMate II LVADs, we developed a method for 3D quantification of IC malpositioning. Using Mimics image software (Materialise, Leuven, Belgium), the native heart, major arteries, and LVAD were segmented to create patient-specific 3D models, allowing LV cavity volume and long-axis length to be measured directly. The deviation of the IC was quantified in a cylindrical coordinate system at the IC insertion point relative to the mitral valve and septum, and IC occlusion was assessed by the distance between cannula inlet and the proximal endocardium. Compared with normal cases, patients with malpositioned pumps had shorter LV length (p = 0.03) and reduced pump pocket depth (p = 0.009). Malpositioned pumps may experience greater obstruction by the nearby myocardium. This quantitative 3D modeling tool may help identify different modes of pump malalignment and migration and may facilitate preoperative planning and minimally invasive approaches via virtual LVAD implantation.

Design and principle of operation of the HeartMate PHP (percutaneous heart pump).

The HeartMate PHP (percutaneous heart pump) is a second-generation transcatheter axial flow circulatory support system. The collapsible catheter pump is inserted through a 14 Fr sheath, deployed across the aortic valve expanding to 24 Fr and able to deliver up to 5 L/min blood flow at minimum haemolytic risk. As such, this device may be a valuable adjunct to percutaneous coronary intervention (PCI) of challenging lesions in high-risk patients or treatment of cardiogenic shock. This technical report discusses: (i) the HeartMate PHP concept, (ii) the implantation technique, (iii) the haemodynamic performance in an in vitro cardiovascular flow testing set-up, and (iv) preliminary clinical experience. An update on the device, produced by St. Jude Medical/Abbott Laboratories, can be found in the Appendix.

Design Rationale and Preclinical Evaluation of the HeartMate 3 Left Ventricular Assist System for Hemocompatibility.

The HeartMate 3 (HM3) left ventricular assist device (LVAD) is designed to support advanced heart failure patients. This centrifugal flow pump has a magnetically levitated rotor, artificial pulse, textured blood-contacting surfaces, optimized fluid dynamics, large blood-flow gaps, and low shear stress. Preclinical tests were conducted to assess hemocompatibility. A computational fluid dynamics (CFD) model guided design for low shear stress and sufficient washing. Hemolysis testing was conducted on six pumps. Plasma-free hemoglobin (PfHb) and modified index of hemolysis (MIH) were compared with HeartMate II (HMII). CFD showed secondary flow path residence times between 27 and 798 min, comparable with main flow residence times between 118 and 587 min; HM3 vs. HMII shear stress exposure above 150 Pa was 3.3 vs. 11 mm within the pump volume and 134 vs. 604 mm on surfaces. In in vitro hemolysis tests at 2, 5, and 10 L/min, average pfHb 6 hours after test initiation was 58, 74, and 157 mg/dl, compared with 112, 123, and 353 mg/dl for HMII. The HM3/HMII ratio of average MIH at 2, 5, and 10 L/min was 0.29, 0.36, and 0.22. Eight 60 day bovine implants were tested with average flow rates from 5.6 to 6.4 L/min with no device failures, thrombosis, or hemolysis. Results support advancing HM3 to clinical trials.

Critical transitions in early embryonic aortic arch patterning and hemodynamics.

Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a temporal window of increased vulnerability to aberrant aortic arch morphogenesis with the potential for profound effects on subsequent cardiovascular morphogenesis.

Fontan conversion templates: patient-specific hemodynamic performance of the lateral tunnel versus the intraatrial conduit with fenestration.

Intraatrial-conduit Fontan is considered a modification of both extracardiac and lateral-tunnel Fontan. In this study, the patient-specific hemodynamic performance of intraatrial-conduit and lateral-tunnel Fontan with fenestration, considered as conversion templates, was investigated based on the authors' patient cohort. Pulsatile computational fluid dynamics simulations were performed using patient-specific models of intraatrial-conduit and lateral-tunnel Fontan patients. Real-time "simultaneous" inferior and superior vena cava, pulmonary artery, and fenestration flow waveforms were acquired from ultrasound. Multiple hemodynamic performance indices were investigated, with particular focus on evaluation of the pulsatile flow performance. Power loss inside the lateral-tunnel Fontan appeared to be significantly higher than with the intraatrial-conduit Fontan for patient-specific cardiac output and normalized connection size. Inclusion of the 4-mm fenestration at a 0.24 L/min mean flow resulted in a lower cavopulmonary pressure gradient and less time-averaged power loss for both Fontan connections. Flow structures within the intraatrial conduit were notability more uniform than within the lateral tunnel. Hepatic flow majorly favored the left lung in both surgical connections: conversion from lateral-tunnel to intraatrial-conduit Fontan resulted in better hemodynamics with less power loss, a lower pressure gradient, and fewer stagnant flow zones along the conduit. This patient-specific computational case study demonstrated superior hemodynamics of intraatrial-conduit Fontan over those of lateral-tunnel Fontan with or without fenestration and improved performance after conversion of the lateral tunnel to the intraatrial conduit. The geometry-specific effect of the nonuniform hepatic flow distribution may motivate new rationales for the surgical design.

Computer modeling for the prediction of thoracic aortic stent graft collapse.

OBJECTIVE: To assess the biomechanical implications of excessive stent protrusion into the aortic arch in relation to thoracic aortic stent graft (TASG) collapse by simulating the structural load and quantifying the fluid dynamics on the TASG wall protrusion extended into a model arch. METHODS: One-way coupled fluid-solid interaction analyses were performed to investigate the flow-induced hemodynamic and structural loads exerted on the proximal protrusion of the TASG and aortic wall reconstructed from a patient who underwent traumatic thoracic aortic injury repair. Mechanical properties of a Gore TAG thoracic endoprosthesis (W. L. Gore and Assoc, Flagstaff, Ariz) were assessed via experimental radial compression testing and incorporated into the computational modeling. The TASG wall protrusion geometry was characterized by the protrusion extension (PE) and by the angle (θ) between the TASG and the lesser curvature of the aorta. The effect of θ was explored with the following four models with PE fixed at 1.1 cm: θ = 10 degrees, 20 degrees, 30 degrees, and 40 degrees. The effect of PE was evaluated with the following four models with θ fixed at 10 degrees: PE = 1.1 cm, 1.4 cm, 1.7 cm and 2.0 cm. RESULTS: The presence of TASG wall protrusion into the aortic arch resulted in the formation of swirling, complex flow regions in the proximal luminal surface of the endograft. High PE values (PE = 2.0 cm) led to a markedly reduced left subclavian flow rate (0.27 L/min), low systolic perfusion pressure (98 mm Hg), and peak systolic TASG diameter reduction (2 mm). The transmural pressure load across the TASG was maximum for the model with the highest PE and θ, 15.2 mm Hg for the model with PE = 2.0 cm and θ = 10 degrees, and 11.6 mm Hg for PE = 1.1 cm and θ = 40 degrees. CONCLUSIONS: The findings of this study suggest that increased PE imparts an apparent risk of distal end-organ malperfusion and proximal hypertension and that both increased PE and θ lead to a markedly increased transmural pressure across the TASG wall, a load that would portend TASG collapse. Patient-specific computational modeling may allow for identification of patients with high risk of TASG collapse and guide preventive intervention. CLINICAL RELEVANCE: A potentially devastating complication that may occur after endovascular repair of traumatic thoracicaortic injuries is stent graft collapse. Although usually asymptomatic, stent graft collapse may be accompanied by adverse hemodynamic consequences. Numerous anatomic and device-related factors contribute to the development of collapse, but predictive factors have not yet been clearly defined. In the present study, we assessed the relevant hemodynamics and solid mechanics underlying stent graft collapse using a computational fluid-structure interaction framework of stent graft malapposition. Our findings suggest that both increased stent graft angle and extension into the aortic arch lead to a markedly increased transmural pressure across the stent graft wall, portending collapse. Patient-specific computational modeling may allow for identification of patients at high risk for collapse and aid in planning for an additional, prophylactic intervention to avert its occurrence.

Pulsatile venous waveform quality in Fontan circulation-clinical implications, venous assists options and the future.

OBJECTIVE: Functionally univentricular heart (FUH) anomalies are the leading cause of death from all structural birth defects. Total cavopulmonary connection (TCPC) is the last stage of the palliative surgical reconstruction with significant late hemodynamic complications requiring high-risk heart transplantation. Alternative therapeutic options for these critically ill patients are crucial. In Phase I, we investigated the effect of pulsatility of venous flow (VF) waveform on the performance of functional and "failing" Fontan (FF) patients based on conduit power loss. In phase 2, the effect of enhanced external counter pulsation on Fontan circulation flow rates is monitored. METHODS: In phase 1, Doppler VFs were acquired from FF patients with ventricle dysfunction. Using computational fluid dynamics (CFD), hemodynamic efficiencies of the FF, functional and in-vitro generated mechanically assisted VF waveforms were evaluated. In phase 2, Fontan circulation on sheep model was created and enhanced external counter pulsation (EECP) applied. RESULTS: Variations in the pulsatile content of the VF waveforms altered conduit efficiency notably. High frequency and low amplitude oscillations lowered the pulsatile component of power losses in FF VF waveforms. The systemic venous flow, pulmonary artery and aorta flows increased by utilizing EECP. CONCLUSION: Our data highlighted the significance of VF pulsatility on energy efficiency inside SV circulation and the feasibility of VF waveform optimization. EECP assist in Fontan circulation can result in venous flow augmentation.

Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo.

In the early embryo, a series of symmetric, paired vessels, the aortic arches, surround the foregut and distribute cardiac output to the growing embryo and fetus. During embryonic development, the arch vessels undergo large-scale asymmetric morphogenesis to form species-specific adult great vessel patterns. These transformations occur within a dynamic biomechanical environment, which can play an important role in the development of normal arch configurations or the aberrant arch morphologies associated with congenital cardiac defects. Arrested migration and rotation of the embryonic outflow tract during late stages of cardiac looping has been shown to produce both outflow tract and several arch abnormalities. Here, we investigate how changes in flow distribution due to a perturbation in the angular orientation of the embryonic outflow tract impact the morphogenesis and growth of the aortic arches. Using a combination of in vivo arch morphometry with fluorescent dye injection and hemodynamics-driven bioengineering optimization-based vascular growth modeling, we demonstrate that outflow tract orientation significantly changes during development and that the associated changes in hemodynamic load can dramatically influence downstream aortic arch patterning. Optimization reveals that balancing energy expenditure with diffusive capacity leads to multiple arch vessel patterns as seen in the embryo, while minimizing energy alone led to the single arch configuration seen in the mature arch of aorta. Our model further shows the critical importance of the orientation of the outflow tract in dictating morphogenesis to the adult single arch and accurately predicts arch IV as the dominant mature arch of aorta. These results support the hypothesis that abnormal positioning of the outflow tract during early cardiac morphogenesis may lead to congenital defects of the great vessels due to altered hemodynamic loading.

Pulsatile venous waveform quality affects the conduit performance in functional and "failing" Fontan circulations.

OBJECTIVE: To investigate the effect of pulsatility of venous flow waveform in the inferior and superior caval vessels on the performance of functional and "failing" Fontan patients based on two primary performance measures - the conduit power loss and the distribution of inferior caval flow (hepatic factors) to the lungs. METHODS: Doppler angiography flows were acquired from two typical extra-cardiac conduit "failing" Fontan patients, aged 13 and 25 years, with ventricle dysfunction. Using computational fluid dynamics, haemodynamic efficiencies of "failing", functional, and in vitro-generated mechanically assisted venous flow waveforms were evaluated inside an idealised total cavopulmonary connection with a caval offset. To investigate the effect of venous pulsatility alone, cardiac output was normalised to 3 litres per minute in all cases. To quantify the pulsatile behaviour of venous flows, two new performance indices were suggested. RESULTS: Variations in the pulsatile content of venous waveforms altered the conduit efficiency notably. High-frequency and low-amplitude oscillations lowered the pulsatile component of the power losses in "failing" Fontan flow waveforms. Owing to the offset geometry, hepatic flow distribution depended strongly on the ratio of time-dependent caval flows and the pulsatility content rather than mixing at the junction. "Failing" Fontan flow waveforms exhibited less balanced hepatic flow distribution to lungs. CONCLUSIONS: The haemodynamic efficiency of single-ventricle circulation depends strongly on the pulsatility of venous flow waveforms. The proposed performance indices can be calculated easily in the clinical setting in efforts to better quantify the energy efficiency of Fontan venous waveforms in pulsatile settings.

Hemodynamics of the hepatic venous three-vessel confluences using particle image velocimetry.

Despite rapid advancements in the patient-specific hemodynamic analysis of systemic arterial anatomies, limited attention has been given to the characterization of major venous flow components, such as the hepatic venous confluence. A detailed investigation of hepatic flow structures is essential to better understand the origin of characteristic abnormal venous flow patterns observed in patients with cardiovascular venous disease. The present study incorporates transparent rapid-prototype replicas of two pediatric hepatic venous confluence anatomies and two-component particle image velocimetry to investigate the primary flow structures influencing the inferior vena cava outflow. Novel jet flow regimes are reported at physiologically relevant mean venous conditions. The sensitivity of fluid unsteadiness and hydraulic resistance to multiple-inlet flow regimes is documented. Pressure drop measurements, jet flow characterization, and blood damage assessments are also performed. Results indicate that the orientation of the inlets significantly influences the major unsteady flow structures and power loss characteristics of this complex venous flow junction. Compared to out-of-plane arranged inlet vessel configuration, the internal flow field observed in planar inlet configurations was less sensitive to the venous inlet flow split. Under pathological flow conditions, the effective pressure drop increased as much as 77% compared to the healthy flow state. Experimental flow field results presented here can serve as a benchmark case for the surgical optimization of complex anatomical confluences including visceral hemodynamics as well as for the experimental validation of high-resolution computational fluid dynamics solvers applied to anatomical confluences with multiple inlets and outlets.

Right ventricular outflow tract reconstruction with bicuspid valved polytetrafluoroethylene conduit.

BACKGROUND: In general, all conduits available for right ventricular outflow tract (RVOT) reconstruction eventually become stenotic or insufficient. Owing to the lack of an ideal conduit and with the hope of reducing the incidence of reoperations, we have developed and utilized a bicuspid valved polytetrafluoroethylene (PTFE) conduit for the reconstruction of the RVOT. The purpose of this study was to review our early experience with this conduit. METHODS: From October 2008 to September 2009, we have implanted bicuspid valved PTFE conduits in 18 patients with a median age of 1.7 years (range 6 days to 16 years). Their diagnoses include tetralogy of Fallot with pulmonary atresia in 8, truncus arteriosus in 6, congenital aortic stenosis in 2, transposition of great arteries in 1, and interrupted aortic arch with a ventricular septal defect in 1. In 16 patients, a complete biventricular repair was performed. In another 2 cases, the conduit was used for palliative RVOT reconstruction. The conduit sizes varied from 10 mm to 24 mm in diameter. Three-dimensional flow fields obtained from computational fluid dynamics studies were utilized in the conduit design process. RESULTS: There was no surgical mortality or reinterventions associated with the PTFE conduit placement in our series. At the time of discharge, none of the patients had any echocardiographic findings consistent with significant conduit stenosis or insufficiency. During the follow-up period of 6.2 ± 3.9 months, all patients were alive and only 3 had more than mild pulmonary insufficiency. CONCLUSIONS: Our bicuspid valved PTFE conduit has an acceptable early performance, with a low incidence of valve insufficiency and no conduit stenosis. Certainly, longer follow-up is necessary to fully assess its long-term benefits.

Computer-Aided Patient-Specific Coronary Artery Graft Design Improvements Using CFD Coupled Shape Optimizer.

This study aims to (i) demonstrate the efficacy of a new surgical planning framework for complex cardiovascular reconstructions, (ii) develop a computational fluid dynamics (CFD) coupled multi-dimensional shape optimization method to aid patient-specific coronary artery by-pass graft (CABG) design and, (iii) compare the hemodynamic efficiency of the sequential CABG, i.e., raising a daughter parallel branch from the parent CABG in patient-specific 3D settings. Hemodynamic efficiency of patient-specific complete revascularization scenarios for right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX) bypasses were investigated in comparison to the stenosis condition. Multivariate 2D constraint optimization was applied on the left internal mammary artery (LIMA) graft, which was parameterized based on actual surgical settings extracted from 2D CT slices. The objective function was set to minimize the local variation of wall shear stress (WSS) and other hemodynamic indices (energy dissipation, flow deviation angle, average WSS, and vorticity) that correlate with performance of the graft and risk of re-stenosis at the anastomosis zone. Once the optimized 2D graft shape was obtained, it was translated to 3D using an in-house "sketch-based" interactive anatomical editing tool. The final graft design was evaluated using an experimentally validated second-order non-Newtonian CFD solver incorporating resistance based outlet boundary conditions. 3D patient-specific simulations for the healthy coronary anatomy produced realistic coronary flows. All revascularization techniques restored coronary perfusions to the healthy baseline. Multi-scale evaluation of the optimized LIMA graft enabled significant wall shear stress gradient (WSSG) relief (~34%). In comparison to original LIMA graft, sequential graft also lowered the WSSG by 15% proximal to LAD and diagonal bifurcation. The proposed sketch-based surgical planning paradigm evaluated the selected coronary bypass surgery procedures based on acute hemodynamic readjustments of aorta-CA flow. This methodology may provide a rational to aid surgical decision making in time-critical, patient-specific CA bypass operations before in vivo execution.

In vitro evaluation of right ventricular outflow tract reconstruction with bicuspid valved polytetrafluoroethylene conduit.

Conduits available for right ventricular outflow tract (RVOT) reconstruction eventually become stenotic and/or insufficient due to calcification. In order to reduce the incidence of reoperations we have developed and used a bicuspid valved polytetrafluoroethylene (PTFE) conduit for the RVOT reconstruction. The purpose of this study is to investigate the hemodynamic performance of the new design using a pediatric in vitro right heart mock loop. PTFE conduit has been used for the complete biventricular repair of 20 patients (age 1.7±6 years) with cyanotic congenital defects. To account for the large variability of conduit sizes, 14, 16, 22, and 24-mm conduit sizes were evaluated using an in vitro flow loop comprised of a pulsatile pump with cardiac output (CO) of 1.2-3.2L/min, bicuspid valved RVOT conduit, pulmonary artery, venous compartments, and the flow visualization setup. We recorded the diastolic valve leakage and pre- and post-conduit pressures in static and pulsatile settings. In vitro valve function and overall hemodynamic performance was evaluated using high-speed cameras and ultrasonic flow probes. Three-dimensional flow fields for different in vivo conduit curvatures and inflow regimes were calculated by computational fluid dynamics (CFD) analysis to further aid the conduit design process. The average pressure drop over the valved conduits was 0.8±1.7mm Hg for the CO range tested. Typical values for regurgitant fraction, peak-to-peak pressure gradient, and effective office area were 23±2.1%, 13±2.4mm Hg, and 1.56±0.2 cm(2) , respectively. High-speed videos captured the intact valve motion with asymmetrical valve opening during the systole. CFD simulations demonstrated the flow skewness toward the major curvature of the conduit based on the pulmonic curvature. In vitro evaluation of the bicuspid valved PTFE conduit coincides well with acceptable early clinical performance (mild insufficiency), with relatively low pressure drop, and intact valve motion independent from the conduit curvature, orientation or valve location, but at the expense of increased diastolic flow regurgitation. These findings benchmark the baseline performance of the bicuspid valved conduit and will be used for future designs to improve valve competency.

Optimization of inflow waveform phase-difference for minimized total cavopulmonary power loss.

The Fontan operation is a palliative surgical procedure performed on children, born with congenital heart defects that have yielded only a single functioning ventricle. The total cavo-pulmonary connection (TCPC) is a common variant of the Fontan procedure, where the superior vena cava (SVC) and inferior vena cava (IVC) are routed directly into the pulmonary arteries (PA). Due to the limited pumping energy available, optimized hemodynamics, in turn, minimized power loss, inside the TCPC pathway is required for the best optimal surgical outcomes. To complement ongoing efforts to optimize the anatomical geometric design of the surgical Fontan templates, here, we focused on the characterization of power loss changes due to the temporal variations in between SVC and IVC flow waveforms. An experimentally validated pulsatile computational fluid dynamics solver is used to quantify the effect of phase-shift between SVC and IVC inflow waveforms and amplitudes on internal energy dissipation. The unsteady hemodynamics of two standard idealized TCPC geometries are presented, incorporating patient-specific real-time PC-MRI flow waveforms of "functional" Fontan patients. The effects of respiration and pulsatility on the internal energy dissipation of the TCPC pathway are analyzed. Optimization of phase-shift between caval flows is shown to lead to lower energy dissipation up to 30% in these idealized models. For physiological patient-specific caval waveforms, the power loss is reduced significantly (up to 11%) by the optimization of all three major harmonics at the same mean pathway flow (3 L/min). Thus, the hemodynamic efficiency of single ventricle circuits is influenced strongly by the caval flow waveform quality, which is regulated through respiratory dependent physiological pathways. The proposed patient-specific waveform optimization protocol may potentially inspire new therapeutic applications to aid postoperative hemodynamics and improve the well being of the Fontan patients.

Pulsatile in vitro simulation of the pediatric univentricular circulation for evaluation of cardiopulmonary assist scenarios.

The characteristic depressed hemodynamic state and gradually declining circulatory function in Fontan patients necessitates alternative postoperative management strategies incorporating a system level approach. In this study, the single-ventricle Fontan circulation is modeled by constructing a practical in vitro bench-top pulsatile pediatric flow loop which demonstrates the ability to simulate a wide range of clinical scenarios. The aim of this study is to illustrate the utility of a novel single-ventricle flow loop to study mechanical cardiac assist to Fontan circulation to aid postoperative management and clinical decision-making of single ventricle patients. Two different pediatric ventricular assist devices, Medos and Pediaflow Gen-0, are anastomosed in two nontraditional configurations: systemic venous booster (SVB) and pulmonary arterial booster (PAB). Optimum ventricle assist device strategy is analyzed under normal and pathological (pulmonary hypertension) conditions. Our findings indicate that the Medos ventricular assist device in SVB configuration provided the highest increase in pulmonary (46%) and systemic (90%) venous flow under normal conditions, whereas for the hypertensive condition, highest pulmonary (28%) and systemic (55%) venous flow augmentation were observed for the Pediaflow ventricular assist device inserted as a PAB. We conclude that mechanical cardiac assist in the Fontan circulation effectively results in flow augmentation and introduces various control modalities that can facilitate patient management. Assisted circulation therapies targeting single-ventricle circuits should consider disease state specific physiology and hemodynamics on the optimal configuration decisions.

Aortic arch morphogenesis and flow modeling in the chick embryo.

Morphogenesis of the "immature symmetric embryonic aortic arches" into the "mature and asymmetric aortic arches" involves a delicate sequence of cell and tissue migration, proliferation, and remodeling within an active biomechanical environment. Both patient-derived and experimental animal model data support a significant role for biomechanical forces during arch development. The objective of the present study is to quantify changes in geometry, blood flow, and shear stress patterns (WSS) during a period of normal arch morphogenesis. Composite three-dimensional (3D) models of the chick embryo aortic arches were generated at the Hamburger-Hamilton (HH) developmental stages HH18 and HH24 using fluorescent dye injection, micro-CT, Doppler velocity recordings, and pulsatile subject-specific computational fluid dynamics (CFD). India ink and fluorescent dyes were injected into the embryonic ventricle or atrium to visualize right or left aortic arch morphologies and flows. 3D morphology of the developing great vessels was obtained from polymeric casting followed by micro-CT scan. Inlet aortic arch flow and cerebral-to-lower body flow split was obtained from 20 MHz pulsed Doppler velocity measurements and literature data. Statistically significant variations of the individual arch diameters along the developmental timeline are reported and correlated with WSS calculations from CFD. CFD simulations quantified pulsatile blood flow distribution from the outflow tract through the aortic arches at stages HH18 and HH24. Flow perfusion to all three arch pairs are correlated with the in vivo observations of common pharyngeal arch defect progression. The complex spatial WSS and velocity distributions in the early embryonic aortic arches shifted between stages HH18 and HH24, consistent with increased flow velocities and altered anatomy. The highest values for WSS were noted at sites of narrowest arch diameters. Altered flow and WSS within individual arches could be simulated using altered distributions of inlet flow streams. Thus, inlet flow stream distributions, 3D aortic sac and aortic arch geometries, and local vascular biologic responses to spatial variations in WSS are all likely to be important in the regulation of arch morphogenesis.