Lipid Shell Retention and Selective Binding Capability Following Repeated Transient Acoustic Microdroplet Vaporization.

Targeted therapy and molecular imaging using ultrasound have been widely explored using microbubble contrast agents, and more recently, activatable droplet contrast agents that vaporize when exposed to focused ultrasound have been explored. These droplets are coated with a stabilizing, functionalizable shell, typically comprised of fully saturated phospholipids. While the shedding of the lipid shell under ultrasound exposure is a well-studied phenomenon in microbubbles, it has not been fully explored in droplet-based contrast agents, particularly in those that undergo a reversible phase change and recondense following vaporization. Here, we investigate the retention of the lipid shell following repeated transient vaporization events. Two separate fluorescent markers were used to track individual lipid subpopulations: PEGylated lipids, to which targeting ligands are typically bound, and non-PEGylated lipids, which primarily contribute to droplet stability. Following confirmation of the homogeneous surface distribution of each subpopulation of shell lipids using confocal microscopy, high-speed optical imaging provided visual evidence of the ability to repeatedly induce vaporization and recondensation in micron-scale droplets using 5.208 MHz, 3.17 MPa focused ultrasound pulses transmitted from an imaging transducer. Flow cytometry analysis indicated that while PEGylated lipids were fully retained following repeated transient phase change events, 20% of the bulk lipids were shed. While this likely contributed to an observed significant reduction in the average droplet diameter, the selective binding capabilities of droplets functionalized with an RGD peptide, targeted to the integrin αvß3, were not affected. These results indicate that repeated droplet activation may promote shifts in the droplet size distribution but will not influence the accuracy of targeting for therapy or molecular imaging.

Role of Vessel Microstructure in the Longevity of End-to-Side Grafts.

Compliance mismatch between the graft and the host artery of an end-to-side (ETS) arterial bypass graft anastomosis increases the intramural stress in the ETS graft-artery junction, and thus may compromise its long-term patency. The present study takes into account the effects of collagen fibers to demonstrate how their orientations alter the stresses. The stresses in an ETS bypass graft anastomosis, as a man-made bifurcation, are compared to those of its natural counterpart with different fiber orientations. Both of the ETS bypass graft anastomosis and its natural counterpart have identical geometric and material models and only their collagen fiber orientations are different. The results indicate that the fiber orientation mismatch between the graft and the host artery may increase the stresses at both the heel and toe regions of the ETS anastomosis (the maximum principal stress at the heel and toe regions increased by 72% and 12%, respectively). Our observations, thus, propose that the mismatch between the collagen fiber orientations of the graft and the host artery, independent of the effect of the suture line, may induce aberrant stresses to the anastomosis of the bypass graft.

Ventricular vortex loss analysis due to various tricuspid valve repair techniques: an ex vivo study.

The deteriorating nature of severe functional tricuspid regurgitation (FTR) has led to the heightened interest in this pathology. However, therapies are heterogeneous and an ideal technique is uncertain. The hemodynamic impact on the cardiac chamber following therapeutic repairs has not been well studied, while its analysis could be used to predict the treatment success. In this study, the hemodynamics of the right ventricle (RV) after 1) clover edge-to-edge tricuspid repair, and 2) double orifice tricuspid repair was evaluated in three right heart models using an ex vivo pulsatile platform emulating severe FTR with the aid of stereoscopic particle image velocimetry. Although all repairs substantially reduced tricuspid regurgitant area, they resulted in a more than 50% reduction in diastolic tricuspid valve (TV) opening area. Splitting the TV orifice into multiple smaller orifices by both repairs eliminated the ring-shaped vortical structure inside the RV observed in FTR cases. Postrepair RV domain was mostly occupied with irregular vortical features and isolated vortex residuals. Moreover, vortical features varied among repair samples, indicating enhanced sensitivity of RV flow to postrepair TV morphology. Compared with clover repair, double orifice subjected the RV to enhanced swirling motions and exposed more regions to vortical motions, potentially indicating better rinsing and lower risk of mural thrombus formation. Double orifice repair increased the levels of RV mean kinetic energy and viscous energy loss than those observed in clover repair, although the impact of these on the cardiac efficiency remains unclear. These preliminary insights could be used to improve future treatment design and planning.NEW & NOTEWORTHY While clover and double orifice tricuspid repairs markedly improved leaflet coaptation, they substantially reduced diastolic tricuspid opening area. Postrepair right ventricle (RV) exhibited specific hemodynamic traits, including the loss of ring-shaped vortical structure and the enhanced sensitivity of RV flow to postrepair tricuspid valve morphology. Compared with clover technique, double orifice repair led to higher swirling motions in the RV domain, which could indicate lower risk of mural thrombus formation.

Design and Development of Novel Transcatheter Bicaval Valves in the Interventional Treatment of Tricuspid Regurgitation.

The concept of heterotopic implantation of transcatheter tricuspid valve is new and has shown promising results thus far. While the Reynolds shear stress values measured in the vicinity of this valve are relatively low, the values at some time points are higher than the threshold of platelet activation. Hence, in this study, we aim to reduce these values with an innovative stent design. It was shown that the Reynolds shear stress values measured were lower than those of valves made of generic stent design and the maximum Reynolds shear stress values in the vicinity of the valves was very low (∼10 dynes/cm2 ). The results also depicted the interesting flow phenomenon of this non-physiological treatment approach. Thus, this study has shown that bicaval valves could potentially be considered as a minimally invasive option to treat tricuspid regurgitation and valve design improvements could reduce the flow disturbances that were observed.

Simulated Bench Testing to Evaluate the Mechanical Performance of New Carotid Stents.

Our group recently developed a novel covered carotid stent that can prevent emboli while preserving the external carotid artery (ECA) branch blood flow. However, our recent in vitro side-branch ECA flow preservation tests on the covered stents revealed the need for further stent frame design improvements, including the consideration to crimp the stent to a low profile for the delivery of the stent system and having bigger cells. Hence, the current work aims to design new bare metal stents with bigger cell size to improve the crimpability and to accommodate more slits so that the side-branch flow could be further increased. Three new stent designs were analyzed using finite element analysis and benchmarked against two commercially available carotid stents in terms of their mechanical performances such as crimpability, radial strength, and flexibility. Results indicated that the new bare metal stent designs matched well against the commercial stents. Hence our new generation covered stents based on these designs can be expected to perform better in side-branch flow preservation without compromising on their mechanical performances.

Covered Stent Membrane Design for Treatment of Atheroembolic Disease at Carotid Artery Bifurcation and Prevention of Thromboembolic Stroke: An In Vitro Experimental Study.

In this study, a polymeric membrane has been designed and developed for carotid stents to prevent detachment of emboli from the arterial wall and subsequent stroke, while maintaining side-branch flow. Prototypes of different geometrical design parameters have been fabricated and their performance has been evaluated in vitro under physiological pulsatile flow condition in a life-size silicone anastomotic model of carotid artery bifurcation. These evaluations include both quantitative and qualitative experimental (in vitro) assessments of emboli prevention capability, side-branch flow preservation, and flow visualization. The covered stents with the novel membrane demonstrated significantly higher emboli prevention capability than the corresponding bare nitinol stent as well as some earlier related designs, while preserving more than 93% of the original flow of the external carotid artery (ECA). Flow in the ECA through these covered stents was uniform without evidence of undesirable flow recirculation or retrograde flow that might predispose the vessel wall to intimal thickening and atherosclerotic plaque formation. This study demonstrated the potential of these novel covered stent designs for the treatment of carotid atherosclerotic stenosis and prevention of late embolic stroke. However, further in vivo investigations of biological effects and mechanical performance of this covered stent design (e.g., its thrombogenicity potential and biocompatibility) are warranted.

Computational Hemodynamic Investigation of Bileaflet and Trileaflet Mechanical Heart Valves.

BACKGROUND AND AIM OF THE STUDY: The trileaflet heart valve is a more desirable mechanical heart valve due to its similarity to native heart valves, which produce a central blood flow with decreased blood flow disturbance. There are, however, many challenges and difficulties in designing a trileaflet valve, mainly due to a greater number of moving mechanical parts. METHODS: The flow profiles through a bileaflet mechanical heart valve (BMHV) and a trileaflet mechanical heart valve (TMHV) were compared at downstream regions. Geometric models of a 29 mm St. Jude Medical BMHV and a TMHV were used and positioned at the anatomic position in a curved aortic downstream geometry. Three-dimensional numerical simulations for both types of mechanical heart valve were performed under normal physiological pulsatile flow conditions. Flow profiles were studied under three different implantation locations at Z = 1D (D = 29 mm inlet diameter), 2D and 4D along the aorta centerline during peak systole. RESULTS: The simulation results showed different flow fields at the downstream positions at Z = 1D and 2D. The leaflets of the BMHV obstructed the flow, while the TMHV allowed a central orifice flow which resulted in a more physiological flow profile. Further downstream, at Z = 4D, the flow fields shared similarities in terms of the flow profile and velocity magnitude. CONCLUSION: The findings of this study may help to further improve the development of the TMHV.

In Vitro Investigation of the Hemodynamics of Transcatheter Heterotopic Valves Implantation in the Cavo-Atrial Junction.

Severe tricuspid regurgitation (TR) is life-threatening but is often undertreated. Many patients with severe TR are denied heart valve replacement surgery because their old age or comorbidities predispose them to a higher risk of surgical complications associated with open-heart surgery. With the advent of transcatheter technology, it is now possible to deliver the valve to the desired location without the need for open-heart surgery. However, presently, there is no commercially available transcatheter tricuspid valve. This may be due to the complex tricuspid valve anatomy, which lacks an anchorage zone for the percutaneous valves. In view of this drawback, we have recently developed and tested two percutaneous caval heart valves that are designed to deploy at the vena cava and atrium junction. The hemodynamic characteristics of these valves are tested in a mock circulatory system with patient-specific silicone atrium and vena cava, which emulates the physiological pressure and flow conditions at the right side of the human heart. Particle imaging velocimetry results showed that flow velocity and the associated Reynolds shear stress (RSS) and the turbulent kinetic energy (TKE) downstream of the valves increased after the implantation of the valves. A maximum flow velocity of 0.94 m/s was observed at the region downstream of the percutaneous valve at the superior vena cava (SVC). Maximum RSS value of 2076.1 dynes/cm(2) was observed downstream of the valve at the inferior vena cava during the deceleration phase while maximum TKE measured was 572.6 J/m(3) at the upstream of the valve in the SVC during the peak flow phase. While these values appear high, they are significantly lower than those reported in prosthetic mitral and aortic valves. Hence, caval stented valves can be potentially considered as a minimally invasive option to treat TR.

Numerical analysis of the hemodynamic performance of bileaflet mechanical heart valves at different implantation angles.

BACKGROUND AND AIM OF THE STUDY: The effects of the implantation angle of bileaflet mechanical heart valves (BMHVs) on the sinus region and downstream flow profiles were investigated. Three-dimensional numerical simulations of BMHVs were performed under physiologic pulsatile flow conditions. The study aim was to examine how the flow fields of different aortic sinus shapes and the downstream aortic arch geometry would be affected by implantation angle. METHODS: Two geometric models of sinus were investigated: a simplified axisymmetric sinus; and a three-sinus aortic root model, with two different downstream geometries, namely a straight pipe and a simplified curved aortic arch. A 29 mm St. Jude Medical BMHV geometric model was used and positioned at four different angles (0 degrees, 30 degrees, 60 degrees and 90 degrees). RESULTS: The simulation results showed variation in downstream flow profiles at different implantation angles. Generally, at position Z = 1D along the centerline (where Z refers to the axis normal to the x-y plane and D is the inlet diameter), the triple-jet structures were observed with a slight shift of the center jet for three-sinus aortic cases. Apparent differences were observed at position Z = 2D and 4D, such as higher velocity profiles at the inner arch wall. The flow field downstream of the valve implanted at 0 degrees (anatomic position) showed the smallest overall asymmetry at peak systole, while the flow field downstream of the valve implanted at 90 degrees (anti-anatomic position) exhibited high regions of recirculation. CONCLUSION: Valve orientation was found not to affect the shear stress distribution significantly in the downstream aorta, and this was in agreement with the findings of earlier studies.

Coronary artery bypass grafting hemodynamics and anastomosis design: a biomedical engineering review.

In this paper, coronary arterial bypass grafting hemodynamics and anastomosis designs are reviewed. The paper specifically addresses the biomechanical factors for enhancement of the patency of coronary artery bypass grafts (CABGs). Stenosis of distal anastomosis, caused by thrombosis and intimal hyperplasia (IH), is the major cause of failure of CABGs. Strong correlations have been established between the hemodynamics and vessel wall biomechanical factors and the initiation and development of IH and thrombus formation. Accordingly, several investigations have been conducted and numerous anastomotic geometries and devices have been designed to better regulate the blood flow fields and distribution of hemodynamic parameters and biomechanical factors at the distal anastomosis, in order to enhance the patency of CABGs. Enhancement of longevity and patency rate of CABGs can eliminate the need for re-operation and can significantly lower morbidity, and thereby reduces medical costs for patients suffering from coronary stenosis. This invited review focuses on various endeavors made thus far to design a patency-enhancing optimized anastomotic configuration for the distal junction of CABGs.

Nondimensional diabetes indices for accurate diagnosis of diabetic subjects.

OBJECTIVES: Nondimensional indices or numbers can provide a generalized approach for integrating several biological parameters into one Nondimensional Physiological Index (NDPI) that can help characterize an abnormal state associated with a particular physiological system. In this paper, we have presented four Nondimensional Physiological Indices (NDI, DBI, DIN, CGMDI) for the accurate detection of diabetes subjects. METHODOLOGY: The NDI, DBI, and DIN diabetes indices are based on the Glucose-Insulin Regulatory System (GIRS) Model, represented by the governing differential equation of blood glucose concentration response to the glucose input rate. The solutions of this governing differential equation are employed to simulate the clinical data of the Oral Glucose Tolerance Test (OGTT), and thereby evaluate the GIRS model-system parameters, which are distinctly different for the normal and diabetic subjects. Then these GIRS model parameters are combined to form singular nondimensional indices: NDI, DBI, and DIN. When these indices are applied to the OGTT clinical data, we get significantly different values for normal and diabetic subjects. The DIN diabetes index is a more objective index involving extensive clinical studies, incorporating the GIRS model parameters as well as some key clinical-data markers (based on the information gained from the model clinical simulation and parametric identification). We have then developed another CGMDI diabetes index based on the GIRS model, for the assessment of diabetic subjects using the glucose levels measured by wearable continuous glucose monitoring (CGM) devices. CLINICAL STUDY AND RESULTS: For the DIN diabetes index, our clinical study comprised of 47 subjects (26 normal and 21 diabetics). After applying DIN to the OGTT data, a Distribution Plot of DIN was developed, displaying the ranges of DIN for (i) normal (i.e., non-diabetic) subjects with no risk of becoming diabetic, (ii) normal subjects at risk of becoming diabetic, (iii) borderline diabetic subjects who can become normal (with diet control and treatment), and (iv) distinctly diabetic subjects. This distribution plot is shown to distinctly separate normal subjects from diabetic subjects and also from subjects at risk of becoming diabetic. CONCLUSIONS: In this paper, we have developed several NDPIs in the form of novel nondimensional diabetes indices for the accurate detection of diabetes and diagnosis of diabetic subjects. These nondimensional diabetes indices can enable precision medical diagnostics of diabetes, and thereby also help to develop interventional guidelines for lowering glucose levels by means of insulin infusion. The novelty of our proposed CGMDI is that it utilizes the glucose value monitored by the CGM wearable device. In the future, an app can be developed to use the CGM data in the CGMDI to enable precision diabetes detection.

Combined gas embolization and chemotherapy can result in complete tumor regression in a murine hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is an intractable cancer with a high mortality rate. Transarterial chemoembolization (TACE), a non-curative method, is the first line therapy for intermediate stage patients. This effectively extends patient survival but requires a complicated intraarterial catheterization procedure and is poorly suited to repeated administration. Here, we investigate gas chemoembolization, a less invasive, more easily administered transient occlusion method that circumvents these limitations. We examined the efficacy of repeated embolization combined with systemically administered doxorubicin, the most common chemotherapeutic in TACE, or tirapazamine, a hypoxia-activated cytotoxic agent, in an ectopic xenograft model of HCC. Emboli were generated in situ using acoustic droplet vaporization, the noninvasive focused ultrasound-mediated conversion of intravenously administered perfluorocarbon microdroplets into microbubbles. Gas embolization alone significantly reduced the Ki67 index and tumor viability (11.6 ± 6.71% non-necrotic vs 100% in control; p < 0.01) after 3 treatments, as assessed by histological analysis. Mice treated for three weeks exhibited significant tumor regression compared to control (23.8 ± 5.37% of initial volume vs 427 ± 49.7% in controls, p < 0.01), irrespective of the chosen chemotherapeutic agent. However, an additional three weeks of monitoring post-treatment elucidated a significant difference in the tumor recurrence rate, with combined gas embolization and doxorubicin resulting in the best treatment outcomes (60% complete regression). While doxorubicin administration resulted in significant cardiotoxicity (p < 0.01), it strongly interacted with the droplet shells, reducing the systemic dose by 11.4%. Overall, gas chemoembolization shows promise as a developmental therapy and merits further study in more complex tumor models.

Effects of left atrium on intraventricular flow in numerical simulations.

With the aid of cardiac imaging techniques, recent numerical simulations of left ventricular flow can be patient-specific to better mimic physiological conditions. However, studies with a dynamic mitral valve (MV) remain extremely limited. Even so, the left atrium (LA) is usually simplified to be tubular regardless of its complex structure. Studies on the effect of this simplification are limited and observations are controversial. In this study, both tubular and generic atriums were incorporated in patient-specific simulations with and without the MV to qualitatively and quantitatively estimate the effects of the atrial model on downstream ventricular flow. The patient-specific model was generated based on cardiac magnetic resonance (CMR) images of a healthy volunteer, and the dynamic motion of the MV was defined by the contours acquired along long-axis images. Based on the simulations, the influence of the atrial vortices on ventricular flow was significant in the valveless models in terms of flow structure, kinetic energy (KE) and circulation. Although these effects were suppressed in the presence of the MV, the atrial vortices that survived the passage were not trivial, which was evidenced by reduced strength of circulation and undesired flow pattern in the apical region. The flow structure in the generic atrium also dominated the development of ventricular flow in the valveless model. After the MV was incorporated, its effects on the downstream ventricular flow were considerably reduced but not eliminated. Therefore, a proper modelling of atrial flow is necessary, especially for subjects with high ejection fraction (EF).

Ex vivo assessment of bicuspidization repair in treating severe functional tricuspid regurgitation: a stereo-scopic PIV study.

There has been a resurgence of interest in the treatment of severe functional tricuspid regurgitation (FTR) due to the awareness of its poor outcomes and potential percutaneous therapies. Kay bicuspidization has been adapted in percutaneous therapies but its clinical outcome remains uncertain. The present study evaluates the efficacy of Kay repair in a novel ex vivo pulsatile system. Porcine tricuspid valve (TV) (n = 3) was extracted and incorporated into a patient-specific silicon right ventricle (RV) emulating severe FTR, on which Kay repair was subsequently performed. TV area metrics and RV hemodynamic assessment by means of stereo-scopic particle image velocimetry were quantified in both FTR and post-repair conditions. Bicuspidization led to significant increase in cardiac output although the overall increment due to this approach alone was generally small, possibly due to existence of residual TR and the large reduction in TV opening area. Kinetic energy and viscous loss levels were increased post-repair, especially during diastolic filling. Main vortex structures generally maintained post-procedural. However, there was enhanced swirling motion in larger RV domain. Although this might reduce mural-thrombus risk, the relatively more complex vortex phenomenon likely resulted in elevated viscous loss observed and may potentially impact long-term adaptation. The RV hemodynamic alteration after tricuspid repair could be used to predict the success of these future transcatheter solutions.

Hemodynamic analysis of a novel stent graft design with slit perforations in thoracic aortic aneurysm.

Thoracic endovascular aortic repair (TEVAR) has been introduced as a less invasive approach to the treatment of thoracic aortic aneurysm (TAA). However, the effectiveness of TEVAR in the treatment of TAA is often limited due to the complex anatomy of aortic arch. Flow preservation at the three supra-aortic branches further increases the overall technical difficulty. This study proposes a novel stent graft design with slit perforations that can positively alter the hemodynamics at the aortic arch while maintaining blood flow to supra-aortic branches. We carried out a computational fluid dynamic (CFD) analysis to evaluate flow characteristics near stented aortic arch in simplified TAA models, followed by in-vitro experiments using particle image velocimetry (PIV) in a mock circulatory loop. The hemodynamics result was studied in terms of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and endothelial cell action potential (ECAP). The results showed that the stent graft with slit perforations can reduce the disturbed flow region considerably. Furthermore, the effect of the slits on flow preservation to the supra-aortic branches was simulated and compared with experimental results. The effectiveness of the stent graft with slit perforations in preserving flow to the branches was demonstrated by both simulated and experimental results. Low TAWSS and elevated ECAP were observed in the aortic arch aneurysm after the placement of the stent graft with slits, implying the potential of thrombus formation in the aneurysm. On the other hand, the effects of the stent grafts with full-slit design and half-slit design on the shear stress did not differ significantly. The present analysis indicated that not only could the stent graft with slit perforations shield the aneurysm from rupture, but also it resulted in a favorable environment for thrombus that can contribute to the shrinkage of the aneurysm.

Minimally invasive gas embolization using acoustic droplet vaporization in a rodent model of hepatocellular carcinoma.

Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. Many patients are not eligible for curative therapies, such as surgical resection of the tumor or a liver transplant. Transarterial embolization is one therapy clinically used in these cases; however, this requires a long procedure and careful placement of an intraarterial catheter. Gas embolization has been proposed as a fast, easily administered, more spatially selective, and less invasive alternative. Here, we demonstrate the feasibility and efficacy of using acoustic droplet vaporization to noninvasively generate gas emboli within vasculature. Intravital microscopy experiments were performed using the rat cremaster muscle to visually observe the formation of occlusions. Large gas emboli were produced within the vasculature in the rat cremaster, effectively occluding blood flow. Following these experiments, the therapeutic efficacy of gas embolization was investigated in an ectopic xenograft model of hepatocellular carcinoma in mice. The treatment group exhibited a significantly lower final tumor volume (ANOVA, p = 0.008) and growth rate than control groups - tumor growth was completely halted. Additionally, treated tumors exhibited significant necrosis as determined by histological analysis. To our knowledge, this study is the first to demonstrate the therapeutic efficacy of gas embolotherapy in a tumor model.

Post-operative ventricular flow dynamics following atrioventricular valve surgical and device therapies: A review.

Intra-ventricular flow dynamics has recently emerged as an important evaluation and diagnosis tool in different cardiovascular conditions. The formation of vortex pattern during the cardiac cycle has been suggested to play important epigenetic and energy-modulation roles in cardiac remodelling, adaptations and mal-adaptations. In this new perspective, flow alterations due to different cardiovascular procedures can affect the long-term outcome of those procedures. Especially, repairs and replacements performed on atrioventricular valves are likely to exert direct impact on intra-ventricular flow pattern. In this review, current consensus around the roles of vortex dynamics in cardiac function is discussed. An overview of physiological vortex patterns found in healthy left and right ventricles as well as post-operative ventricular flow phenomenon owing to different atrioventricular valvular procedures are reviewed, followed by the summary of different vortex identification schemes used to characterise intraventricular flow. This paper also emphasises on future research directions towards a comprehensive understanding of intra-cardiac flow and its clinical relevance. The knowledge could encourage more effective pre-operative planning and better outcomes for current clinical practices.

Gas Embolization in a Rodent Model of Hepatocellular Carcinoma Using Acoustic Droplet Vaporization.

Trans-arterial embolization is a commonly used therapy in unresectable hepatocellular carcinoma. Current methods involve the careful placement of an intraarterial catheter and the deposition of embolizing particles. Gas embolotherapy has been proposed as an embolization method with the potential for high spatial resolution without the need for a catheter. This method involves vaporizing intravenouslyadministered droplets into gas bubbles using focused ultrasound - a process termed acoustic droplet vaporization. The bubbles can become lodged in the vasculature, thereby creating an embolus. Here, we initially demonstrate the feasibility of achieving significant targeted embolization with this method in the rat cremaster using intravital microscopy. The therapy was then tested in an ectopic xenograft mouse model of hepatocellular carcinoma. Gas embolotherapy was shown to maintain the tumor volume at baseline over a twoweek treatment course while control groups showed significant tumor growth. These preliminary results demonstrate thatgas embolotherapy could serve as an effective noninvasive method for the management of unresectable hepatocellular carcinoma.

Experimental Study of Right Ventricular Hemodynamics After Tricuspid Valve Replacement Therapies to Treat Tricuspid Regurgitation.

The increased understanding of right heart diseases has led to more aggressive interventions to manage functional tricuspid regurgitation (FTR). In some cases of FTR, prosthetic valve replacement is typically considered when concomitant organic components or significant geometrical distortions are involved in the pathology of the tricuspid valve. However, little is known of the performance of current devices in the right heart circulation. In this study, a novel in vitro mock circulatory system that incorporated a realistic tricuspid valve apparatus in a patient-specific silicon right ventricle (RV) was designed and fabricated. The system was calibrated to emulate severe FTR, enabling the investigation of RV hemodynamics in pre- and post-implantation of tri-leaflet tissue implant and bi-leaflet mechanical implant. 2D particle imaging velocimetry was performed to visualize flow and quantify relevant hemodynamic parameters. While our results showed all prosthetic implants improved cardiac output, these implants also subjected the RV to increased turbulence level. Our study also revealed that the implants did not create the optimal behavior of fluid transfer in the RV as we expected. Among the implants tested, tissue implant created the most dominant vortices, which persisted throughout diastole; its observed strong negative vortex could lead to increase energy expenditure due to undesired fluid direction. In contrast, both native valve and mechanical implant had both weaker vortex formation as well as more significant vortex dissipation. Interestingly, the vortex dissipation of native valve was associated with streamlined flow pattern that tended towards the pulmonary outlet, while the mechanical implant generated more regions of flow stagnation within the RV. These findings heighten the imperative to improve designs of current heart valves to be used in the right circulation.

Hemodynamic assessment of extra-cardiac tricuspid valves using particle image velocimetry.

There has not been much progress in the development of transcatheter tricuspid valves to treat tricuspid regurgitation because of the difficulty in anchoring a stented valve onto the complex tricuspid annulus. Hence, the concept of heterotopic implantation of the transcatheter tricuspid valve onto the cavo-atrial junction was proposed. However, to date there has been no detailed in vitro investigation of the hemodynamic performance of this new device. The study utilises both 2-D and 3-D particle image velocimetry (PIV) to interrogate the flow patterns in the vicinity of the extra-cardiac tricuspid valves in an in vitro physiological flow loop, specifically at four measurement locations in the cavo-atrial anatomy. Comparison of the 2-D and 3-D PIV results revealed that accuracy of 2-D PIV would be acceptable at time point and at measurement locations where the velocity was mostly planar with minimal or low out-of-plane flow such as at the outlet of the superior vena cava valve at the point of valve closure. The results also showed that the RSS in the vicinity of the valves were relatively low (∼150 dynes/cm2) with the exception of that in the leakage jet at the upstream of the valve. The leakage in the leaflets could be a result of the use of aortic valve leaflets which was more suited for the higher pressured environment of the left side of the heart. The stent design could also be customised for implantation in the vena cava. In summary, these issues could be eradicated with improvements to the leaflet and stent design which would enhance the haemodynamics of the post-implantation flow performance.