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Aortic insufficiency (AI) is a common complication that increases morbidity and mortality in patients with left ventricular assist devices (LVAD). Significant AI during LVAD support creates a substantial regurgitant flow loop, negatively affecting cardiac recovery and exposing blood to longer residence time and higher shear stress. The mechanism of AI development and progression is linked to a lack of aortic valve opening, which alters the valvular tissue mechanics. Pre-existing AI also worsens following LVAD implantation, interfering with the pump benefits. This chapter will evaluate AI development with LVAD support compared with naturally occurring AI and present the features, mechanisms, and links to clinical treatment options.

Improper left ventricular assist device (LVAD) inflow cannula (IC) positioning creates areas of stasis and low pulsatility that predispose thromboembolism, but may be mitigated with LVAD speed modulation. A mock loop study was performed to assess the sensitivity of left ventricle (LV) flow architecture to IC position and speed modulation during HeartMate3 support. System pressure, flow, and the time-resolved velocity field were measured within a transparent silicone LV for three IC angles and three IC insertion depths at matched levels of cardiac function and LVAD speed. Inflow cannula angulation towards the septum increased the resistance to LVAD flow as well as increasing the size and energy of the counter-clockwise (CCW) vortex. Apical velocity was reduced compared to IC angulation towards the mitral valve, but regional pulsatility was maintained across all angles and LVAD speeds. Increased IC protrusion decreased LVAD flow resistance, increasing velocity within the IC but reducing flow and pulsatility in the adjacent apical region. Increasing LVAD flow resistance improves aortic valve opening and strengthens the CCW vortex which directs inflow towards the septum, producing higher blood residence time and shear activation potential. Despite this impact on flow architecture, pulsatility reduction with increased LVAD speed was minimal with the HeartMate3 speed modulation feature.

During left ventricular assist device (LVAD) support, the external work performed by the native heart combines with the work performed by the rotary LVAD to provide cyclic flow through the LVAD and, in some conditions, through the aortic valve. In this study, a balance of external work was developed and validated for both full and partial bypass conditions that includes valve opening and aortic compliance.The theory assumes a steady-state contribution of external work from the rotary LVAD and a dynamic portion from the heart. Cyclic flow may be ejected through either the LVAD or ascending aorta, and an energy absorption term accounts for aortic compliance. Mock loop studies were performed for LV ejection fractions of 10%-28% combined with HeartMate II LVAD support at 8 and 11 krpm to produce a range of full and partial bypass conditions. The external work of the LVAD and native heart was computed from the experimental pressure-flow (H-Q) relations and compared to the theory.Native heart contraction produces a counterclockwise loop in the pressure-flow relation of the LVAD which increased with ejection fraction, and during full bypass conditions the external work was preserved in the total systemic flow. During partial bypass conditions, forward flow through the ascending aorta was accompanied by a reversal during aortic valve closure resulting in a reduction in energy in the downstream flow.The study presents a balance of external work during full and partial bypass LVAD support. Experimental data validated the additional terms corresponding to forward flow and aortic compliance that contribute to the system balance. This expanded theory can be applied to LVAD design and control to improve pulsatility and aortic valve biomechanics.

Dilated cardiomyopathy produces abnormal left ventricular (LV) blood flow patterns that are linked with thromboembolism (TE). We hypothesized that implantation of mechanical heart valves non-trivially influences TE risk in these patients, exacerbating abnormal LV flow dynamics. The goal of this study was to assess how mitral valve design impacts flow and hemodynamic factors associated with TE. The mid-plane velocity field of a silicone dilated LV model was measured in a mock cardiovascular loop for three different mitral prostheses, two with multiple orientations, and used to characterize LV vortex properties through the cardiac cycle. Blood residence time and a platelet shear activation potential index (SAP) based on the cumulative exposure to shear were also computed. The porcine bioprosthesis (BP) and the bileaflet valve in the anti-anatomical (BL-AA) position produced the most natural flow patterns. The bileaflet valves experienced large shear in the valve hinges and recirculating shear-activated flow, especially in the anatomical (BL-A) and 45-degree (BL-45) positions, thus exhibited high SAP. The tilting disk valve in the septal orientation (TD-S) produced a complete reversal of flow and vortex properties, impairing LV washout and retaining shear-activated fluid, leading to the highest residence time and SAP. In contrast, the tilting disk valve in the free-wall position (TD-F) exhibited mid-range values for residence time and SAP. Hence, the thrombogenic potential of different MHV models and configurations can be collectively ranked from lowest to highest as: BP, BL-AA, TD-F, BL-A, BL-45, and TD-S. These findings provide new insight about the effect of fluid dynamics on LV TE risk, and suggest that the bioprosthesis valve in the mitral position minimizes this risk by producing more physiological flow patterns in patients with dilated cardiomyopathy.

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.

Stroke is a devastating complication of cardiovascular surgeries, and the risk is particularly high for those requiring cardiopulmonary bypass (CPB). Embolic particles generated during the unclamping of the aortic cross-clamp may enter the cerebral circulation, lodging in small vessels. External manual compression of the carotid arteries is a non-invasive technique that has been proposed for cerebral protection during CPB procedures but is not widely deployed. The aim of this study is to assess the potential for cerebral emboli reduction with carotid compression using an in vitro model. Experiments were performed with a glass aortic arch model in a mock cardiovascular circuit. Small fluorescent particles were released into the circulation with and without carotid compression, and the particles visualized in the aortic midplane. The number of particles in the aorta and arch branch vessels were counted from the images before, during and following the release of carotid compression for durations of 10, 15 and 20 s. A gamma variate function was fit to the data to describe the bolus dynamics. Carotid compression for 10 s reduces the number of embolic articles entering the carotid arteries by over 75%. A compression duration of 15–20 s does not result in greater particle reduction than one of 10 s. Brief compression of the common carotid arteries during cardiovascular interventions has the potential to dramatically reduce the number of cerebral emboli and should be investigated further.

Left ventricular assist device (LVAD) inflow cannula malposition is a significant risk for pump thrombosis. Thrombus development is influenced by altered flow dynamics, such as stasis or high shear that promote coagulation. The goal of this study was to measure the intraventricular flow field surrounding the apical inflow cannula of the Evaheart centrifugal LVAD, and assess flow stasis, vortex structures, and pulsatility for a range of cannula insertion depths and support conditions. Experimental studies were performed using a mock loop with a customized silicone left ventricle (LV) and the Evaheart LVAD. A transparent inflow cannula was positioned at 1, 2, or 3 cm insertion depth into the LV and the velocity field in the LV midplane was measured for 2 levels of LVAD support: 1800 and 2300 rpm. The LV velocity field exhibits a diastolic vortex ring whose size, path, and strength are affected by the flow conditions and cannula position. During diastole, the large clockwise midplane vortex grows, but its circulation and kinetic energy are reduced with cannula insertion depth. The counterclockwise vortex is smaller and exhibits more complex behavior, reflecting a flow split at 3 cm. Overall, the 1 cm cannula insertion depth produces the flow pattern that exhibits the least apical flow stasis and greatest pulsatility and should correlate to a lower risk of thrombus formation.

Purpose Aortic valve incompetence (AI) is a serious complication that develops in 20% of LVAD patients within 12 months of implantation. Many LVAD patients with AI also develop mitral regurgitation (MR). Our goal in this study was to measure systemic flow (Qsys) and LVAD flow (QLVAD) during AI, MR and AI+MR. Methods A mock circulatory loop with a dilated silicone LV and bioprosthetic valves was attached to a HeartMate II LVAD (Abbott Labs), and pressure and flow measured in the LV, LVAD and aorta. A Pre-LVAD ejection fraction of 20% without any valve dysfunction was established, followed LVAD support at speeds of 8, 9.4 and 11krpm. AI and MR were created with small stents that were non-obstructive to forward flow but prevented the leaflets from fully closing. Four conditions were tested: Normal, AI, MR and AI and MR combined. Average flow was obtained from ten cycles of data, and Q calculated as QLVAD/Qsys. Results Pre-LVAD AI, MR and AI+MR produced a 28%, 12% and 45% reduction in Qsys, respectively. LVAD support at 9.4krpm increased Normal Qsys to 3.6 L/min with 95% of flow through the LVAD. MR reduced Qsys by 16% and QLVADby 21%; AI reduced by Qsys by 24% but QLVADby only 5%; and AI+MR reduced Qsys by 25% and QLVADby 7%, which was comparable to AI alone. In all conditions except AI+MR, Q increases with LVAD speed indicating that QLVAD increases faster than Qsys. This trend reverses when MR is present, reducing the impact of AI as LVAD speed is increased. Conclusion The major finding of these studies is that MR does not worsen Qsys when it coincides with AI and LVAD support. AI and MR occur during different phases of the cardiac cycle and sum in the absence of LVAD support. When an LVAD is added without valve dysfunction, QLVADis evenly distributed across systole and diastole. AI and MR reduces systolic and increases diastolic QLVAD, but AI+MR restores the original distribution. AI+MR produces the same overall Qsys but QLVADoccurs more evenly throughout the cardiac cycle resulting in a greater sensitivity to LVAD speed changes.

The orientation and design of bileaflet valve prosthesis in the mitral position affects the intraventricular blood flow and exposure to shear. The combination of the anatomic orientation and a small gap size of the St. Jude Medical valve produces an increase in shear exposure and blood residence time, which both predispose the formation of thrombus in the high shear gaps of the valve hinges.

Left ventricular assist devices (LVADs) are mechanical pumps that are surgically attached to the left ventricle and aorta. Clinical studies show that LVADs improve patient health and quality of life, and dramatically reduce the mortality of cardiac failure. During periods of high LVAD support, blood flow occurs entirely through the LVAD, the aortic valve is continuously closed, and the heart operates in series with the pump. Thus the normal fluid dynamics of intraventricular flow are altered and linked to the development of thrombus in both the native heart and LVAD. Our goal in this study was to simulate a patient with a recurring thrombus and quantify the variations in the flow field in the LV as the thrombus developed. Particle image velocimetry measurements of transparent silicone models were performed for a range of LVAD support conditions. Results show that the presence of a small thrombus in the LVOT creates a favorable condition for further growth, especially in the presence of high LVAD support. As the thrombus enlarges, it begins to affect the normal vortex-flow pattern, further reducing flow rate and pulsatility in the LVOT. Evaluation of vortex dynamics and stasis regions in both patients and experimental models of LVAD support yield quantitative metrics that can be used to assess the risk of thrombus and the development of strategies to reduce this risk in LVAD patients.

Permanent closure of the aortic valve (AVC) is sometimes performed In LVAD patients, usually when a mechanical valve prosthesis or significant aortic insufficiency is present. Mitral valve regurgitation (MVR) present at the time of LVAD implantation can remain unresolved, representing a limitation for exercise tolerance and a potential predictor of mortality. To investigate the effect of MVR on hemodynamics of the LVAD-supported heart following AVC, studies were performed using a mock circulatory loop. Pressure and flow measured for a range of cardiac function, LVAD speed, and MVR show that cardiac contraction augments aortic pressure by 10-27% over nonpulsatile conditions when the mitral valve functions normally, but decreases with MVR until it reaches the nonpulsatile level. Aortic flow displays a similar trend, demonstrating a 25% decrease from fully functioning to open at 7 krpm, a 5% decrease at 9 krpm, and no observable effect at 11 krpm. Pulsatility decreases with increased LVAD speed and MVR. The data indicate that a modest level of cardiac output (1.5-2 L/min) can be maintained by the native heart through the LVAD when the LVAD is off. These results demonstrate that MVR decreases the augmentation of forward flow by improved cardiac function at lower LVAD speeds. While some level of MVR can be tolerated in LVAD recipients, this condition represents a risk, particularly in those patients that undergo AVC closure, and may warrant repair at the time of surgery.

Purpose In patients with left ventricular assist device (LVAD), aortic valve insufficiency (AI) could occur in longer period during the cardiac cycle, throughout the diastolic and part of the isovolumetric phases. As the result, the current echocardiographic evaluation of AI grade may underestimate the degree of AI in LVAD patients, especially those with significant AI. In this study, we investigated the differences in AI duration and regurgitant volume before and during LVAD supports (Off and On LVAD) using a mock circulatory loop. Methods All measurements were performed using a mock circulatory system with a dilated silicone LV model attached to a HeartMate II LVAD (Abbott Lab), and pressure and flow measured in the LV, LVAD, and aorta. Baseline condition was established as no LVAD condition (Off LVAD setting) which has 17% ejection fraction, 62 bpm heart rate and 65 mmHg systemic pressure. LVAD condition (On LVAD setting) at 8,800 rpm with same ejection fraction, heart rate and systemic resistance (90 mmHg systemic pressure) was established, followed by testing at three AI severity conditions. AI severity was defined as mild, moderate, or severe based on effective regurgitant orifice area. AI conditions were created with small 3-D printed stents, which were nonobstructive to forward flow, but prevented the leaflets from fully closing. AI durations and regurgitant volumes were determined from the calculated backward flow through the aortic valve. Results With the constant systemic resistance in the On LVAD setting at 8,800 rpm, duration of AI increased by 8.3 % (75 to 83.3%) with mild AI, 5.6% (77.8 to 83.3%) with moderate AI, and 5.6% (77.8 to 83.3%) with severe AI compared to the Off LVAD setting. With the constant systemic resistance in the On LVAD setting at 8,800 rpm, regurgitant volume of AI increased by 0.11 L/min (0.12 to 0.23 L/min, 92%) in mild AI, 0.03 L/min (0.53 to 0.56 L/min, 5.7%) in moderate AI and 0.08L/min (0.78 to 0.86 L/min, 10.3%) with severe AI compared to the Off LVAD setting. Conclusion This mock loop study demonstrated that AI duration was longer and regurgitant volume through the aortic valve was greater during LVAD support compared to same AI degree before LVAD. This suggests that clinical burden of AI may be underestimated in patients with LVAD.

Due to the high stroke rate of left ventricular assist device (LVAD) patients, reduction of thrombus has emerged as an important target for LVAD support. Left ventricular blood flow patterns with areas of flow stasis and recirculation are associated with platelet aggregation, which is worsened by exposure to high shear stress. Previous reports of intraventricular thrombus in LVAD patients have identified the outside of the LVAD inflow cannula as a nidus for LV thrombus formation. Previous studies of LVAD inflow cannula design have shown a region of low blood velocity and pulsatility at the apex, adjacent to the cannula. One unresolved question is whether the standard practice of inserting the LVAD inflow cannula several mm into the LV could be revised to reduce thrombus formation. To address this, a "tipless" inflow cannula was designed for the EVAHEART LVAS, and assessed in a mock circulatory loop of the LVAD-supported heart. Customized transparent silicone models of a dilated LV were connected to the EVAHEART LVAS at the apex with a clear polycarbonate inflow cannula for flow visualization using particle image velocimetry (PIV). The "tipless" cannula was inserted flush with the endocardial border and did not protrude into the LV. This condition was compared to the standard cannula position with a 1-cm insertion into the LV. The Pre-LVAD condition corresponded to a severe heart failure patient (ejection fraction of 24%) with a dilated LV (180 mL). LVAD support was provided at speeds of 1.8 and 2.3 krpm. At the lower LVAD speed, 63% of the flow passed through the LVAD, with the remainder ejecting through the aortic valve. When LVAD speed was increased, nearly all flow (98%) left the LV through the LVAD. Both LVAD speed conditions produced a vortex ring similar to the Pre-LVAD condition in diastole. However, the protruding inflow cannula interrupted the growth and restricted the movement of the vortex, and produced areas of low velocity and pulsatility adjacent to the cannula. The tipless cannula exhibited an uninterrupted pattern of the mitral jet toward the LV apex, which allowed the diastolic vortex to grow and aid in the washout of this region. In addition, the tipless cannula increased aortic valve flow, which reduces stasis in the left ventricular outflow tract. The EVAHEART LVAS tipless inflow cannula design improved regional velocity, pulsatility, and vortex formation compared to the standard protruding design, which all reduce the risk of thrombus formation. The clinical significance of the differences observed in the flow field will be dependent on other factors such as the cannula material and surface characteristics, as well as the patients' coagulation status.

Previous studies have identified left ventricular assist device (LVAD) inflow cannula (IC) malposition as a significant risk for pump thrombosis. Thrombus development is a consequence of altered flow dynamics, which can produce areas of flow stasis or high shear that promote coagulation. The goal of this study was to measure the effect of IC orientation on the left ventricle (LV) flow field using a mock circulatory loop, and identify flow-based indices that are sensitive measures of cannula malposition. Experimental studies were performed with a customized silicone model of the dilated LV and the EVAHEART Centrifugal LVAS (Evaheart, Inc.; Houston TX). The velocity field of the LV midplane was measured for a transparent IC oriented parallel to and rotated 15° toward the septum under matched hemodynamic conditions. Vortex structures were analyzed and localized stasis calculated within the IC and combined with a map of normalized pulsatile velocity. The velocity fields revealed increased apical stasis and lower pulsatility with a small angulation of the IC. A significant change in vortex dynamics with the angled IC was observed, doubling the size of the counterclockwise (CCW) vortex while reducing the kinetic energy provided by LVAD support. A significant decrease in average and systolic velocities within the IC was found with cannula angulation, suggesting an increased resistance that affects primarily systolic flow and is worsened with increased LVAD support. These common echocardiographic indices offer the opportunity for immediate clinical application during ramp study assessment. Optimized IC positioning may be determined preoperatively using imaging techniques to develop patient-specific surgical recommendations.

Aortic valve opening (AVO) during left ventricular assist device (LVAD) support aids in preventing valve fusion, incompetence, and thrombosis. The programmed low speed algorithm (PLSA) allows AVO intermittently by reducing continuous motor speed during a dwell time. AVO and hemodynamics in the LVAD-assisted heart were measured using a HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD with a PLSA controller in a mock circulatory loop. Left ventricle and aortic pressures, LVAD, and total aortic flow were measured during pre-LVAD, non-PLSA and PLSA combinations of cardiac function, and LVAD speed. The low cardiac setting corresponded to a pre-LVAD cardiac output of 2.8 L/min, stroke volume of 40 ml, and ejection fraction of 22%; the medium setting produced values of 3.5 L/min, 50 ml, and 28%, respectively. Results show that the PLSA controller set at 10 krpm, dropping to 7 krpm for dwell time of 6 s, adequately produced AVO for all tested cardiac functions with only minimal changes in cardiac output. However, AVO frequency was independent of opening area and systolic duration, which both decreased with increasing LVAD support. Furthermore, aortic pulsatility index quadrupled in the aortic root and doubled in the distal aorta during PLSA conditions, providing evidence that AVO and blood mixing are enabled by PLSA control at the appropriate speed.

Left ventricular assist device (LVAD) support disrupts the natural blood flow path through the heart, introducing flow patterns associated with thrombosis, especially in the presence of medical devices. The aim of this study was to quantitatively evaluate the flow patterns in the left ventricle (LV) of the LVAD-assisted heart, with a focus on alterations in vortex development and stasis. Particle image velocimetry of a LVAD-supported LV model was performed in a mock circulatory loop. In the Pre-LVAD flow condition, a vortex ring initiating from the LV base migrated toward the apex during diastole and remained in the LV by the end of ejection. During LVAD support, vortex formation was relatively unchanged although vortex circulation and kinetic energy increased with LVAD speed, particularly in systole. However, as pulsatility decreased and aortic valve opening ceased, a region of fluid stasis formed near the left ventricular outflow tract. These findings suggest that LVAD support does not substantially alter vortex dynamics unless cardiac function is minimal. The altered blood flow introduced by the LVAD results in stasis adjacent to the LV outflow tract, which increases the risk of thrombus formation in the heart.

Purpose Aortic valve (AoV) insufficiency (AI) is a serious complication in more than 20% of Left Ventricle Assist Device (LVAD) patients within 12 months of LVAD implantation. Normal AoV have developed AI following long-term LVAD support,which has been associated with a significant reduction in LVAD patient survival. During LVAD support, the AoV pressure difference is increased, which reduces systolic opening and worsens regurgitant flow through an incompetent valve. The goal of this study was to measure the effect of LVAD support on intraventricular flow during AI. Methods The velocity field was measured in the midplane of a dilated silicone LV model attached to a rotary LVAD (Abbott Labs, Chicago IL) in a mock circulatory loop. A Pre-LVAD without AI condition (BL) of 20% ejection fraction was established, followed by testing at three LVAD speeds. AI was created with a small 3-D printed stent which was nonobstructive to forward flow but prevented the leaflets from fully closing. LV and aortic pressure, and LVAD and distal aortic flow, were recorded. Results At the Pre-LVAD BL condition, the mean aortic pressure was 63 mmHg and the cardiac output was 2.3 L/min; AI maintained a similar pressure but reduced flow to 1.8 L/min producing a 32% regurgitant fraction (mild-moderate AI). At an LVAD speed of 6400rpm, total systemic flow was 4.3 L/min and 3.1 L/min for BL and AI, respectively, and LVAD flow was 4.2 and 3.6 L/min, producing a 45% regurgitant fraction (moderate-severe AI). The reduction of systemic flow was accompanied by higher LVAD flow, confirming that a regurgitant loop was present. Net forward flow through AoV during BL decreased progressively by 23%, 12% and 0.5% for 4800, 5400, and 6400rpm respectively. AI reduced forward flow and increased backward flow, such that net forward flow was 0.5%, -14%, and -17% at 4800, 5400 and 6400rpm. The AI vena contracta width increased from 2.3 to 3.4 mm as LVAD speed increased. Conclusion Overall, the results showed that an initially mild level of AI worsened with LVAD support prior to any remodeling, simply due to the altered biomechanics of the AoV. These findings provide a foundation for new strategies that can restore AoV biomechanics and reduce the impact of AI on patients with LVAD support.

The design of medical devices requires an understanding of a large number of factors, many of which are difficult to teach in the traditional educational format. This subject benefits from using a challenge-based learning approach, which provides focused design challenges requiring students to understand important factors in the context of a specific device. A course was designed at San Diego State University (CA, USA) that applied challenge-based learning through in-depth design challenges in cardiovascular and orthopedic medicine, and provided an immersive field, needs-finding experience to increase student engagement in the process of knowledge acquisition. The principles of US FDA 'design control' were used to structure the students' problem-solving approach, and provide a format for the design documentation, which was the basis of grading. Students utilized a combination of lecture materials, industry guest expertise, texts and readings, and internet-based searches to develop their understanding of the problem and design their solutions. The course was successful in providing a greatly increased knowledge base and competence of medical device design than students possessed upon entering the course.

The increased applicability and excellent results with left ventricular assist devices (LVADs) have revolutionized the available treatment options for patients with advanced heart failure. Pre-existing valve abnormalities are common in this population, and subsequent development of valve abnormalities after LVAD placement is also often noted. Although native mitral and tricuspid valve disease is more common in heart failure patients before LVAD placement, aortic valves are much more likely to generate abnormal pathophysiology in the LVAD patient during as well as after LVAD placement. The aim of this comprehensive review is to review aortic valve function in LVAD patients and highlight the consideration of pre-existing valve disease on patient treatment at the time of LVAD implant. The basis for structural changes leading to valve pathophysiology during and after LVAD placement will be described, providing a basis for improved clinical understanding and new strategies to prevent these conditions.

In patients at risk of intraventricular thrombosis, the benefits of chronic anticoagulation therapy need to be balanced with the pro-hemorrhagic effects of therapy. Blood stasis in the cardiac chambers is a recognized risk factor for intracardiac thrombosis and potential cardiogenic embolic events. In this work, we present a novel flow image-based method to assess the location and extent of intraventricular stasis regions inside the left ventricle (LV) by digital processing flow-velocity images obtained either by phase-contrast magnetic resonance (PCMR) or 2D color-Doppler velocimetry (echo-CDV). This approach is based on quantifying the distribution of the blood Residence Time (TR) from time-resolved blood velocity fields in the LV. We tested the new method in illustrative examples of normal hearts, patients with dilated cardiomyopathy and one patient before and after the implantation of a left ventricular assist device (LVAD). The method allowed us to assess in-vivo the location and extent of the stasis regions in the LV. Original metrics were developed to integrate flow properties into simple scalars suitable for a robust and personalized assessment of the risk of thrombosis. From a clinical perspective, this work introduces the new paradigm that quantitative flow dynamics can provide the basis to obtain subclinical markers of intraventricular thrombosis risk. The early prediction of LV blood stasis may result in decrease strokes by appropriate use of anticoagulant therapy for the purpose of primary and secondary prevention. It may also have a significant impact on LVAD device design and operation set-up.

In the mitral valve, regional variations in structure and material properties combine to affect the biomechanics of the entire valve. Previous biaxial testing has shown that mitral valve leaflet tissue is highly extensible, and exhibits nonlinear, anisotropic material properties. In this study, experimental measurements of mitral valve leaflet deformation under quasi-static pressure loading were performed on isolated porcine hearts. Biplane video images of markers placed on the anterior leaflet surface were used to reconstruct the 3D position of the markers at several pressure levels over the physiological range. A least-squares finite-element method was used to fit parametric models to the markers and to calculate the deformation over the surface. The results showed that the leaflet deformations were anisotropic, exhibiting a large nonhomogeneous radial stretch and a small circumferential stretch. This information can be used to better understand how the valve deforms under physiological loading, and to help design treatments for valve problems, such as mitral regurgitation.

Biaxial testing, histological measurements and theoretical continuum mechanics modeling were employed to investigate the structure and mechanical properties of the mitral valve leaflet-strut chordae transition zone (LCT). The results showed that geometry changes and collagen fiber angle distribution contribute to variations in mechanical properties in the LCT zone. A simple three-coefficient exponential constitutive law was able to simulate the variation in stress-stretch behavior in the LCT zone by spatially varying a single coefficient and incorporating collagen fiber angle and degree of alignment. This quantitative information can greatly improve the predictions from biomechanical valve models by incorporating regional variations of structure and properties in the mitral leaflet-chordae tendineae system. These data provide the foundation for a computational model for studying stress distributions before and following chordal rupture, which may indicate the underlying reasons for the development of valve insufficiency in patients.

The goal of this study was to evaluate the effect of surgical anastomosis configuration of the aortic outflow conduit (AOC) from a continuous flow left ventricular assist device (LVAD) on the flow fields in the aorta using CFD simulations. The geometry of the surgical integration of the LVAD is an important factor in the flow pattern that develops both in series (aortic valve closed, all flow through LVAD) and in parallel (heart pumping in addition to LVAD).CFD models of the AOC junctions simulate geometry as cylindrical tubes that intersect at angles ranging from 30 degrees to 90 degrees. Velocity fields are computed over a range of cardiac output for both series and parallel flow.Our results demonstrate that the flow patterns are significantly affected by the angle of insertion of the AOC into the native aorta, both during series and parallel flow conditions. Zones of flow recirculation and high shear stress on the aortic wall can be observed at the highest angle, gradually decreasing in size until disappearing at the lowest angle of 30 degrees. The highest velocity and shear stress values were associated with series flow.The results suggest that connecting the LVAD outflow conduit to the proximal aorta at a shallower angle produces fewer secondary flow patterns in the native cardiovascular system.

Myocardial contrast echocardiography (MCE) has potential value in the assessment and quantitation of myocardial perfusion defects. However, the severity of stenosis detectable by MCE and its diagnostic accuracy remain undefined. Thus, we produced coronary stenoses of variable severity and quantified their effect on MCE.Three grades of left anterior descending (LAD) obstructions were produced in 7 open-chest swine. The stenoses were nonflow-limiting at rest, but decreased coronary hyperemia by 31.3% +/- 4.7%, 69.9% +/- 5.3% and 98.9% +/- 1.1%, respectively. Regional myocardial blood flow (RBF) was measured with fluorescent microspheres and was expressed as the ratio of LAD and control (LCx) beds. MCE was performed with 0.3 mg/kg intravenous AF0150 during ECG-gated harmonic imaging in short-axis view. Background-subtracted peak intensity (PI) was expressed as the ratio of LAD/LCx beds. Both RBF and PI ratios progressively decreased with increasing grades of stenosis. MCE showed a significant correlation with RBF (r = 0.74; P.0001). Ratios of both PI and RBF differed significantly from baseline when coronary hyperemia was reduced more than 50%. An LAD/LCx ratio less than 0.6 by MCE yielded 61% and 83% sensitivity and 85% and 76% specificity with stenosis that reduced coronary hyperemia more than 50% and more than 75%, respectively.MCE with intravenous AF0150 during vasodilation correctly depicted the progressive reduction of flow ratios produced by graded coronary stenoses. A significant reduction of PI ratio was observed with stenosis causing more than 50% reduction of coronary hyperemia. An MCE ratio in stenosed/control beds could be selected, which exhibited good sensitivity and specificity in the identification of coronary stenosis.

To investigate the effects of water exchange on quantification of perfusion, data were acquired in isolated hearts (n = 11) and used to develop a model of exchange. Myocardial T 1 was measured 3 times/sec during step changes in concentration of intravascular (polylysine-gadolinium-diethylene-triamine-pentaacetic acid) and extracellular (gadoteridol) agents. For the intravascular agent, the change in 1/T 1 (ΔR 1 ) was lower than predicted by fast exchange (2.7 ± 0.5 vs. 7.8 sec -1 , respectively), and suggested an intra-extravascular exchange rate of 3 Hz. For the extracellular agent, contrast kinetics were similar to those of similarly sized molecules (wash-in time constant 38 ± 5 sec), and the data suggested fast interstitial-cellular exchange. Modeling showed that perfusion is underestimated for both agents if exchange is ignored, although the relationships of measured to actual perfusion were monotonic. We conclude that myocardial water exchange strongly affects first-pass enhancement but that ignoring the effects of exchange may still provide reasonable estimates of regional perfusion differences.

All previous studies of residual strain in the ventricular wall have been based on one- or two-dimensional measurements. Transmural distributions of three-dimensional (3-D) residual strains were measured by biplane radiography of columns of lead beads implanted in the midanterior free wall of the canine left ventricle (LV). 3-D bead coordinates were reconstructed with the isolated arrested LV in the zero-pressure state and again after local residual stress had been relieved by excising a transmural block of tissue. Nonhomogeneous 3-D residual strains were computed by finite element analysis. Mean ± SD ( n = 8) circumferential residual strain indicated that the intact unloaded myocardium was prestretched at the epicardium (0.07 ± 0.06) and compressed in the subendocardium (−0.04 ± 0.05). Small but significant longitudinal shortening and torsional shear residual strains were also measured. Residual fiber strain was tensile at the epicardium (0.05 ± 0.06) and compressive in the subendocardium (−0.01 ± 0.04), with residual extension and shortening, respectively, along structural axes parallel and perpendicular to the laminar myocardial sheets. Relatively small residual shear strains with respect to the myofiber sheets suggest that prestretching in the plane of the myocardial laminae may be a primary mechanism of residual stress in the LV.

A case report is presented of a left ventricular assist device (LVAD) recipient with a pre-existing thrombus that was removed on LVAD implant but quickly reformed and was removed, reformed again, and ultimately embolized, causing death. The thrombus formed proximal to the left ventricular outflow tract, because of the presence and subsequent repair of a calcified left ventricular infarct which had extruded from the septum. This region is vulnerable to flow stasis during LVAD support as predicted by experimental fluid mechanics studies, because of the lack of opening of the aortic valve. The presence of the repair and the altered flow field contributed to blood stasis and thrombus growth in a positive feedback loop. Although LVADs provide tremendous benefits for patients by reducing the symptoms of heart failure, the accompanying changes have some secondary consequences that remain problematic. One of these is an abnormal intraventricular flow field that decreases washout, especially in the region proximal to the left ventricular outflow tract, which is an area of flow stasis.

Changes in coronary perfusion pressure lead to alterations in intracoronary myocardial volume that may be associated with regionally altered microvascular morphology. Transmural variations in coronary capillary geometry were quantified as a function of coronary perfusion pressure in glutaraldehyde-fixed canine hearts. Capillary volume fraction, diameter, numerical density, anisotropy, and sarcomere length were measured using computer analysis of light microscopic images of sections taken transverse or longitudinal to the muscle fiber axis. Capillary volume was 4-6% of myocardial wall volume and exhibited a significant transmural gradient, increasing from epicardium to endocardium. Vessels 4 to 5 μm in diameter with a density of 2900 mm -2 appear to increase in diameter and alter their cross-sectional shape with increasing pressure, rather than increasing in number, suggesting an effective distensibility of approximately 0.007 mm Hg -1 . Quantification of vessel anisotropy was directly related to cross sectional shape and demonstrated that the capillaries are highly oriented. These findings indicate that intramyocardial capacitance is at least in part associated with nonhomogeneous changes in coronary capillary morphology with altered perfusion pressure.

Anterior and posterior leaflets from excised porcine mitral valves were mechanically tested under cyclic equibiaxial and strip biaxial stretch protocols at a strain rate of 4-12%/s after preconditioning. Cauchy stress and Lagrangian strain were calculated for both membrane and three-dimensional cases. The leaflets exhibited nonlinearly elastic, anisotropic behavior. Both anterior and posterior leaflets were less extensible in the circumferential than in the radial direction under equibiaxial stretch, with stress ratios of 5.7 and 4.3, respectively. The posterior leaflets exhibited greater extensibility in both directions and lower circumferential posttransitional moduli (ranges 690-820 vs. 2,500-3,200 N/m for anterior). This larger posterior extensibility may be due to the greater number of chordal attachments, which provide additional mechanical stability to this structure. Coupling of radial and circumferential mechanical behavior was evidenced by the response to different stretch protocols, indicating a complex microstructural coupling between individual collagen fibers or bundles. These are the first biaxial data for mitral valves and are a foundation for the development of a more detailed quantitative material description.

The "garden hose" effect of coronary perfusion on diastolic left ventricular (LV) mechanics has been proposed to cause changes in systolic function by altering diastolic sarcomere length. We measured transmural distributions of three-dimensional shape change using radiopaque markers implanted in the LV free wall of eight isolated arrested canine hearts as functions of coronary arterial perfusion pressure (Pp) and LV pressure (PLV) and related these deformations to the local muscle fiber architecture. Increased Pp from 0 to 110 mm Hg produced a 10% reduction in LV chamber volume (P < .01) and 25% to 40% decreases in local three-dimensional wall strain at matched PLV, indicating myocardial stiffening. Significant decreases in the magnitudes of local deformation occurred preferentially in the cross-fiber and radial directions (P < .02), with no change in fiber strain. This suggests that changing coronary Pp does not alter diastolic fiber length; hence, the Frank-Starling law may not mediate the Gregg effect. Since the myocardial microvessels are primarily oriented parallel to the muscle fibers, the observed myocardial stiffening occurs in the directions transverse to the microvessels rather than along their length. Local myocardial wall volume in the unloaded LV demonstrated a uniform 5% increase from the unperfused state to Pp of 50 mm Hg. With further increases in Pp up to 110 mm Hg, the change in regional wall volume from the unperfused state developed a substantial transmural gradient increasing by 7% at the epicardium and 15% at the subendocardium. This reflects a significant increase (P < .02) in intramyocardial coronary capacitance from epicardium to endocardium, which may be related to a transmural gradient in coronary distensibility or vascularity.

Intravenous catheterization is the most common invasive medical procedure today and is designed to introduce medication directly into the blood stream. Common practice is to administer medicine with one syringe, followed by a saline flush to clear the line of any residual medication. The risk of infection due to the introduction of bacteria in the catheter hub is increased with the number of times the hub is accessed. In addition, the two-step process adds millions of nursing hours per year and is prone to error. The goal of this effort was to design and test a dual-chamber syringe that could be reliably used for both dispensing medicine and the saline flush, and be produced at a low cost. The syringe has a novel dual-chamber design with a proximal chamber for medicine and a distal chamber that contains saline. The saline chamber has a fixed volume when the handle is locked into position, which allows the handle to control the variable volume of the medicine chamber. Between the two chambers is a plunger that surrounds the small channel (which is an extension of the distal chamber) that separates the saline from the medicine. When the distal chamber is unlocked, the handle controls the volume of the saline chamber. By this mechanism, the syringe is able inject the medicine followed by the saline flush with a single access to the catheter hub. The smooth operation of the device relies on a locking mechanism to control the rear plunger and volume of the distal saline chamber, and a bubble plug residing in the small channel between the chambers that prevents mixing of the medicine and saline fluids. The bubble plug is held in place by a balance of forces that depend on geometric variables and fluid properties. The chosen design prevents mixing of the two fluids during the operation of the device, which was experimentally validated with mass spectrometry. The dual-chamber syringe has successfully achieved the design goal of a single syringe for the two-step catheter procedure of dispensing medicine and a saline flush. This novel design will reduce the potential for catheter-based infection, medical errors, medical waste, and clinician time. Preliminary test results indicate that this innovation can significantly improve the safety and efficiency of catheter-based administration of medicine.

Aortic valve commissural fusion is a process in which fibrous tissue is deposited at the aortic valve commissures, creating adhesion between leaflets and preventing opening. Fusion has recently been associated with the implantation of left ventricular assist devices (VADs), affecting upwards of 50% of patients in recent studies. Aortic incompetence has also been associated with pulsatile VAD use, but a specific structural mechanism has not been identified. The study aim was to measure aortic valve geometry and fusion in tissue samples from explanted hearts of VAD recipients and to identify features that might explain the development of aortic valve dysfunction.The diameter, perimeter and thickness of the aortic root, as well as the height, edge length and thickness of each of the three aortic leaflets were measured in seven valves. Histological studies were performed of both fused and unfused leaflets.The aortic root geometry showed an elliptical aorta, with asymmetric leaflets. The right coronary leaflet had the greatest edge length, but was thinnest. The other two leaflets were smaller, but slightly thicker. Overall, the aorta and valve geometry was within the normal range. Fusion was found in five of the seven valves studied, and often observed in multiple leaflets. Fusion length correlated loosely with the time of VAD support. Tissue from both fused and unfused valves showed unilateral fibrosis in the leaflets, and a loss of the laminar tissue structure that was related to the duration of VAD support.These findings support previous observations that pathological changes occur in the aortic valves of VAD patients shortly after implantation. While the tissue exhibits abnormalities in the structure, the geometry does not show gross remodeling such as annular dilatation or leaflet lengthening that might precede the development of aortic valve dysfunction. These changes are associated with the development of aortic valve fusion, and may be related to the biomechanical changes introduced by the VAD.

Aortic valve integrity is crucial for optimal left ventricular assist device (LVAD) support. Pre-existing native aortic insufficiency, aortic valve incompetence acquired during support, as well as previously placed prosthetic aortic valves present unique problems for these patients.We reviewed and analyzed data for 28 patients who underwent left ventricular outflow tract closure associated with HeartMate I (n =12) and HeartMate II (n = 16) LVAD insertion or exchange. Indications for valve closure, surgical technique, LVAD function, survival rates and complications were retrospectively analyzed. Survival rates were compared with those of HeartMate LVAD patients (n = 104) who did not undergo aortic valve closure.Indications for closure included native aortic valve insufficiency (10 patients), aortic valve deterioration after prolonged LVAD support (8 patients) and previously placed mechanical (9 patients) or bioprosthetic aortic prostheses (1 patient). There were 2 operative and 5 late deaths (mean 227 days post-operatively). Of the deaths, none were due to aortic valve closure. Actuarial survival was 78% at 1 year and 53% at 3 years, which was statistically better than for our patients with an intact aortic outflow (61% at 1 year, 45% at 3 years; p0.05). Five patients had transplants, 1 patient was successfully bridged to recovery, and 15 patients remain on LVAD support. No patient with outflow closure developed regurgitation, embolization or compromised LVAD support.Outflow tract closure in LVAD-supported patients is safe, often necessary and well tolerated.

A ventricular assist device (VAD) is a pump surgically connected to the heart and aorta in order to boost systemic blood flow in heart failure patients. The design of these devices has evolved over the past 30 years, with improvements and innovations enabled through the synergistic use of experimental research, clinical studies, and computational models. The application of computational fluid dynamics models has allowed the design of VADs to shift from large, bulky devices designed for patients with severe cardiac failure to a variety of smaller devices designed for a range of patients and cardiovascular conditions.

The objective of the present study was to perform biaxial testing and apply constitutive modeling to develop a strain energy function that accurately predicts the material behavior of the aortic valve leaflets. Ten leaflets from seven normal porcine aortic valves were biaxially stretched in a variety of protocols and the data combined to develop and fit a strain energy function to describe the material behavior. The results showed that the nonlinear anisotropic behavior of the aortic valve is well described by a strain energy function of two strain invariants, which uses only three coefficients to accurately predict the stress-strain behavior over a wide range of deformations. This structurally-motivated constitutive law has many applications, including computational modeling for clinical and engineering valve treatments.

There is evidence that the incidence of aortic valve incompetence (AI) and other valvular pathologies may increase as more patients are submitted to longer periods of ventricular assist device (VAD) support. There is a need to better understand the mechanisms associated with the onset of these conditions and other possible complications related to the altered hemodynamics of VAD patients. In this study, the effect of AI on the hemodynamic response of continuous flow VAD (C-VAD) patients was measured in a mock loop over a range of pump speeds and level of native cardiac function. Our results showed that, in the presence of sufficient ventricular function, decreasing the C-VAD speed can allow a transition from series to parallel flow. Our study demonstrated that AI reduces the aortic pressure and flow when system impedance is unchanged. AI produces wasteful recirculation that substantially increases the pump work and decreases systemic perfusion, in particular during series flow conditions coupled with higher C-VAD speeds. The hematologic consequence of this regurgitant flow is a much higher exposure to shear for the blood, increasing the likelihood of hemolysis and thrombosis. While a certain degree of AI can be tolerated by a heart with good cardiac function, the consequences of AI for patients with VADs and poor cardiac function are much greater. Valve dysfunction in VAD patients may be related to structural changes in the tissue induced by altered biomechanics and excessive stress.

Computational fluid dynamics (CFD) models were developed to investigate the altered fluid dynamics of the native aorta in patients with a left ventricular assist device (LVAD). The objective of this study was to simulate the effect of LVAD aortic outflow conduit location on the 3-D flow in the native aorta over a range of boundary conditions. The fluid mechanics of three different surgical geometries [(P), proximal, (D), distal and (IP), in-plane] were studied and the implications for short- and long-term medical consequences explored by evaluating the flow fields, wall shear, and hemolysis. The greatest disruptions in the normal aortic flow pattern occurred with series flow conditions, when flow through the aortic valve was minimal. Under series conditions, circulation in the proximal aorta is retrograde, originating from the LVAD outflow conduit. The (P) geometry provided the most blood washout of the proximal aorta, with a larger region of slow-moving flow observed in the (D) and (IP) models. Wall shear stress was reduced for the (IP) geometry, which lacks the direct flow impingement present in the (P) and (D) models. Clinically, the (D) and (IP) geometries require less traumatic surgeries and probably are better tolerated by the patient. In this situation, the (IP) geometry suggests improvement in both increased flow to the proximal aorta and decreased shear stress compared with (D). However, the (D) and (IP) configurations are not recommended for patients with low or no flow from the heart because of the lack of blood washout near the aortic valve and therefore possible thrombus formation in that area.

Strut chordae transection (SCT) has been recommended as a surgical treatment for mitral regurgitation (MR) arising from ischemic heart disease. However, little is known about the contribution of anterior strut chordae to leaflet tissue mechanics. In this study, experimental measurements of mitral valve deformation under quasi-static pressure loading were performed on isolated pig hearts before and after transecting both strut chordae. Biplane video images of markers placed on the anterior leaflet surface were used to reconstruct the 3D position of the markers. The 2D nonhomogeneous deformations in the anterior leaflet were calculated by least squares fit to the 3D marker coordinates in successive pressure loading states. Results show that the anterior leaflet undergoes large, anisotropic and nonhomogeneous deformation, with a significant radial stretch gradient and smaller, uniform circumferential stretch. Following chordal transection, the radial deformation decreases. A gradient in the circumferential stretch is observed as an increase from the annulus toward the coaptation line. Without the support provided by the strut chordae, the center portion of the anterior leaflet experienced a substantial change in shape in response to the systolic pressure, altering the load-bearing mechanism in the valvular structure. The shift of the deformation distribution suggests that additional strain energy is absorbed by the circumferentially oriented collagen fibers following SCT and may result in long-term tissue remodeling. This study provides detailed biomechanical data for interpreting the results of previous investigations of SCT, as well as for exploring a greater understanding of how SCT affects MR through computational modeling.

Background —The purpose of this study was to verify whether endothelin A–antagonist administration at the time of coronary reperfusion preserves postischemic microvasculature and whether myocardial contrast echo (MCE) is able to detect pharmacologically induced changes in microvascular reflow. Methods and Results —Twenty dogs underwent 90 minutes of LAD occlusion (OCC) followed by 180 minutes of reperfusion (RP). Five minutes before LAD reopening, an intravenous bolus (5 mg/kg) of LU 135252 was given in 10 dogs and vehicle in the remaining 10. At baseline (BSL), OCC, and 90 and 180 minutes of RP, microvascular flow (BF) was assessed by microspheres, and MCE was performed with intravenous echo contrast. MCE videointensity and BF were expressed as risk area/control ratio. Myocardial thickness of the risk area was calculated by 2D echo. No differences in BF between the 2 groups were observed at BSL, OCC, and 90 minutes of RP. At 180 minutes of RP, BF was decreased in controls (70±7.4% of BSL; P P =NS versus BSL; P P Conclusions —Endothelin A–antagonist treatment at the time of reperfusion significantly limited the progressive decrease in postischemic microvascular reflow and the increase in myocardial thickness. MCE allowed a reliable evaluation of pharmacologically induced changes in microvascular flow.

Altered coronary perfusion can change the apparent diastolic stiffness of ventricular myocardium--the 'garden hose' effect. Our recent findings showed that myocardial strains are reduced during ventricular filling, primarily along the directions transverse to the coronary microvessels. In this article, we review hypotheses and theoretical models regarding the role that regional wall stress plays in the mechanical interaction between myocardium and coronary circulation. Various mechanisms have been used to explain the effects of the tissue stress on coronary flow, as well as the effect of coronary dynamics on myocardial mechanics. Many models of coronary pressure-flow relations using lumped parameter circuit analogs. Poroelasticity and swelling theories have been used to model the mechanics of perfused muscle. Here, we describe a new mathematical model of the mechanics of perfused myocardium derived using homogenization theory. In this model, perfused myocardium is treated as a nonlinear anisotropic elastic solid embedded with cylindrical vessels of known distensibility. The solid compartment is incompressible but the vascular compartment may change volume according to a simple relation between vessel diameter and perfusion pressure. The work done by the perfusion pressure in changing vascular volume contributes to the macroscopic strain energy and hence affects the stress and stiffness of the composite. Conversely, the stress in the tissue affects microvessel diameter and volume, since tractions transverse to the vessel axis oppose the internal blood pressure. Finite element simulations of passive filling show good agreement of model with experimental results.

Background. Dynamic changes of myocardial blood flow have been observed after reperfusion of an occluded coronary artery. MCE performed by intracoronary contrast injection can provide an estimate of microvascular flow. We hypothesized that MCE performed using intravenous infusion of a new generation contrast agent and electrocardiogram-gated harmonic imaging would be able to assess serial changes of microvascular perfusion. Objective. To study the potential of myocardial contrast echocardiography (MCE) to assess serial changes of microvascular flow during ischemia-reperfusion. Methods. Sixteen dogs underwent 90 or 180 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Regional blood flow (RBF) was measured with fluorescent microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180 min during reperfusion. At the same time points, MCE was performed with intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Background-subtracted videointensity measured from MCE and RBF obtained from fluorescent microspheres were calculated for the risk area and for a control area, and were expressed as the ratio of the two areas. Results. After initial hyperemia, a progressive reduction in flow was observed during reperfusion. MCE correctly detected the time course of changes in flow during occlusion-reperfusion. Videointensity ratio significantly correlated with RBF data (r = 0.79; p Conclusions. The progressive reduction in blood flow occurring within the postischemic microcirculation was accurately detected by MCE. This approach has potential application in the evaluation and management of postischemic reperfusion in humans.