Lakshmi Prasad Dasi

Hemocompatibility of Superhemophobic Titania Surfaces

The hemocompatibility of superhemophobic surfaces is investigated and compared with that of hemophobic surfaces and hemophilic surfaces. This analysis indicates that only those superhemophobic surfaces with a robust Cassie-Baxter state display significantly lower platelet adhesion and activation. It is envisioned that the understanding gained through this work will lead to the fabrication of improved hemocompatible, superhemophobic medical implants.

On the Mechanics of Transcatheter Aortic Valve Replacement.

Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers.

Aortic sinus flow stasis likely in valve-in-valve transcatheter aortic valve implantation

Objective: Valve‐in‐valve procedures using transcatheter aortic valves are increasingly performed to treat degenerated bioprosthetic surgical aortic valves because they are less invasive than redo aortic valve replacement. The objective of this study is to quantify the changes in aortic sinus blood flow dynamics before and after a valve‐in‐valve procedure to gain insight into mechanisms for clinical and subclinical thrombosis of leaflets. Methods: A detailed description of the sinus hemodynamics for valve‐in‐valve implantation was performed in vitro. A Medtronic Hancock II (Medtronic Inc, Minneapolis, Minn) porcine bioprosthesis was modeled as a surgical aortic valve, and Medtronic CoreValve and Edwards Sapien (Edwards Lifesciences, Irvine, Calif) valves were used as the transcatheter aortic valves. High‐resolution particle image velocimetry was used to compare the flow patterns from these 2 valves within both the left coronary and noncoronary sinuses in vitro. Results: Velocity and vorticity within the surgical valve sinuses reached peak values of 0.7 m/s and 1000 s−1, with a 70% decrease in peak fluid shear stress near the aortic side of the leaflet in the noncoronary sinus. With the introduction of transcatheter aortic valves, peak velocity and vorticity were reduced to approximately 0.4 m/s and 550 s−1 and 0.58 m/s and 653 s−1 without coronary flow and 0.60 m/s and 631 s−1 and 0.81 m/s and 669 s−1 with coronary flow for the CoreValve and Sapien valve‐in‐valve implantations, respectively. Peak shear stress was approximately 38% higher along the aortic side of the coronary versus noncoronary transcatheter aortic valve leaflet. Conclusions: Decreased flow and shear stress in valve‐in‐valve procedures indicate a higher risk of leaflet thrombosis secondary to flow stasis, perhaps more so in the noncoronary sinus.

An In-Vitro Evaluation of Turbulence after Transcatheter Aortic Valve Implantation

Background This study aimed at assessment of post‐transcatheter aortic valve (TAV) replacement hemodynamics and turbulence when a same‐size SAPIEN 3 (Edwards Lifesciences Corp, Irvine, Calif) and Medtronic Evolut (Minneapolis, Minn) were implanted in a rigid aortic root with physiological dimensions and in a representative root with calcific leaflets obtained from patient computed tomography scans. Methods TAV hemodynamics were studied by placing a SAPIEN 3 26‐mm and an Evolut 26‐mm in rigid aortic roots and representative root with calcific leaflets under physiological conditions. Hemodynamics were assessed using high‐fidelity particle image velocimetry and high‐speed imaging. Transvalvular pressure gradients (PGs), pinwheeling indices, and Reynolds shear stress (RSS) were calculated. Results (1) PGs obtained with the Evolut and the SAPIEN 3 were comparable among the different models (10.5 ± 0.15 mm Hg vs 7.76 ± 0.083 mm Hg in the rigid model along with 13.9 ± 0.19 mm Hg vs 5.0 ± 0.09 mm Hg in representative root with calcific leaflets obtained from patient computed tomography scans respectively); (2) more pinwheeling was found in the SAPIEN 3 than the Evolut (0.231 ± 0.057 vs 0.201 ± 0.05 in the representative root with calcific leaflets and 0.366 ± 0.067 vs 0.122 ± 0.045 in the rigid model); (3) higher rates of RSS were found in the Evolut (161.27 ± 3.45 vs 122.84 ± 1.76 Pa in representative root with calcific leaflets and 337.22 ± 7.05 vs 157.91 ± 1.80 Pa in rigid models). More lateral fluctuations were found in representative root with calcific leaflets. Conclusions (1) Comparable PGs were found among the TAVs in different models; (2) pinwheeling indices were found to be different between both TAVs; (3) turbulence patterns among both TAVs translated according to RSS were different. Rigid aortic models yield more conservative estimates of turbulence; (4) both TAVs exhibit peak maximal RSS that exceeds platelet activation 100 Pa threshold limit.

Impact of patient-specific morphologies on sinus flow stasis in transcatheter aortic valve replacement: An in vitro study

Objective The goal of this study is to evaluate how sinus flow patterns after transcatheter aortic valve replacement in realistic representative patient roots vary. Sinus flow can affect transcatheter aortic valve operation and likely leaflet thrombosis occurrence due to stasis and poor washout. How the interaction between transcatheter aortic valve and representative patient aortic roots affects sinus hemodynamics is important to establish for future individualization of transcatheter aortic valve replacement therapy. Methods Two representative patient aortic roots were selected, segmented and 3‐dimensional printed followed by deployment of Medtronic CoreValve (Medtronic Inc, Irvine, Calif) and Edwards SAPIEN (Edwards Lifesciences, Irvine Calif) transcatheter aortic valves. Sinus hemodynamics were assessed in vitro using high spatio‐temporal resolution particle‐image‐velocimetry. Detailed sinus vortex tracking, shear stress probability density functions, and sinus washout were evaluated and assessed as a function of valve type and representative patient morphology as independent case studies. Results Peak velocity in the sinus with SAPIEN valve was approximately 3 times higher than with CoreValve for both models (0.30 ± 0.02 m/s and 0.34 ± 0.041 m/s vs 0.13 ± 0.01 m/s and 0.10 ± 0.02 m/s) (P < .01). Between representative patient models, vorticity magnitudes were significantly different (75 ± 1.1 s−1, 77 ± 3.2 s−1, 109 ± 2.3 s−1, and 250 ± 4.1 s−1) (P < .01) regardless of valve type. Sinus blood washout characteristic as a function of cardiac cycles was strongly both patient related and valve specific. Fluid dynamics favored shear stresses and washout characteristics due to a smaller sinus and sinotubular junction, further amplified by the SAPIEN valve. Conclusions Sinus flow dynamics are highly sensitive to aortic root characteristics and transcatheter aortic valve aortic root interaction. Differences in sinus‐flow washout and stasis regions between representative patient models may be reflected in different risks of leaflet thrombosis or valve degeneration.

Effect of severe bioprosthetic valve tissue ingrowth and inflow calcification on valve-in-valve performance

While in vivo studies clearly demonstrate that supra-annular Valve-in-Valve (ViV) implantation provides the highest probability for optimal post-ViV pressure gradients (PG), there is still no physical insight into explaining anomalies where some supra-annular ViV implantations yield high pressure gradients while some sub-annular implantations yield low pressure gradients. The aim of this study is to explain how severe tissue ingrowth and calcification (TIC) in a surgical aortic valve (SAV) can be one physical mechanism leading to anomalous ViV performance characteristic. The ViV hemodynamic performance was evaluated as a function of axial positioning -9.8, -6.2, 0, and +6 mm in SAVs with and without TIC. Effective orifice area (EOA) and PG were compared. Leaflet high-speed imaging and particle image velocimetry were performed to elucidate flutter and forward jet characteristics. ViV without TIC showed significantly lower PG and greater EOA (p < 0.01). EOA and PG improve with supra-annular deployment (p < 0.01) while for ViV with TIC, EOA and PG worsen as the deployment varies from -9.8 mm to 0 mm (p < 0.01) only to recover at + 6 mm (p < 0.01). Separated jet flow at the TIC site, and consequently induced stronger TAV leaflet fluttering highlight the dynamic compromising nature of TIC on jet width and performance reduction. We conclude that the inflow TIC greatly influence ViV performance due to dynamic effects that results in a real anomalous performance characteristic different than that seen in most ViV in vivo. Further in vivo studies are needed to evaluate ViV outcomes in the presence of severe TIC in SAVs.

Effect of Arched Leaflets and Stent Profile on the Hemodynamics of Tri-Leaflet Flexible Polymeric Heart Valves

Polymeric heart valves (PHV) can be engineered to serve as alternatives for existing prosthetic valves due to higher durability and hemodynamics similar to bioprosthetic valves. The purpose of this study is to evaluate the effect of geometry on PHVs coaptation and hemodynamic performance. The two geometric factors considered are stent profile and leaflet arch length, which were varied across six valve configurations. Three models were created with height to diameter ratio of 0.6, 0.7, and 0.88. The other three models were designed by altering arch height to stent diameter ratio, to be 0, 0.081, and 0.116. Particle image velocimetry experiments were conducted on each PHV to characterize velocity, vorticity, turbulent characteristics, effective orifice area, and regurgitant fraction. This study revealed that the presence of arches as well as higher stent profile reduced regurgitant flow down to 5%, while peak systole downstream velocity reduced to 58% and Reynolds Shear Stress values reduced 40%. Further, earlier reattachment of the forward flow jet was observed in PHVs with leaflet arches. These findings indicate that although both geometric factors help diminish the commissural gap during diastole, leaflet arches induce a larger jet opening, yielding to earlier flow reattachment and lower energy dissipation.

Stented valve dynamic behavior induced by polyester fiber leaflet material in transcatheter aortic valve devices

OBJECTIVE This study aims at assessing the global dynamic behavior, elastic deformability, closing energy and turbulence of rigid versus deformable stented (RS vs DS) valve systems with deformable and rigid textile materials (DT vs RT) through studying the stent-valve interaction compared to a bioprosthetic material in transcatheter aortic valves (TAV). METHODS Three 19 mm stented textile TAV designs (RS-DT, RS-RT and DS-RT) with different stent and leaflet properties were tested and compared with a control bioprosthetic TAV (RS-DB) in a left heart simulator flow loop under physiological pressure and flow. Particle Image Velocimetry and high speed imaging were performed. Pressure gradients (PG), leakage fractions (LF), Pinwheeling indices (PI), closing energy (E) and Reynolds shear stresses (RSS) were calculated. RESULTS (a) PGs and LFs were 11.86 ± 0.51 mmHg, 11.70 ± 0.34%; 8.84 ± 0.40 mmHg, 29.80 ± 0.76%; 11.59 ± 0.12 mmHg, 14.23 ± 1.64%; and 7.05 ± 0.09 mmHg, 12.08 ± 0.45% % for RS-DB, RS-DT, RS-RT and DS-RT respectively. (b) PIs were 15.79 ± 2.34%, 4.36 ± 0.84%, 2.47 ± 0.51% and 2.03 ± 0.33% for RS-DB, RS-DT, RS-RT and DS-RT respectively. (c) E is lowest for DS-RT (0.0010 ± 0.0002 J) followed by RS-RT (0.0017 ± 0.0002 J), RS-DB (0.0023 ± 0.0004 J) and highest with RS-DT (0.0036 ± 0.0007 J). (d) At peak systole lowest RSS was obtained with RS-DT (87.82 ± 0.58 Pa) and highest with DS-RT (122.98 ± 1.87 Pa). CONCLUSION PGs, LFs, PIs and E were improved with DS-RT compared to other textile TAVs and RS-DB. Despite achieving more RSS than the rest of TAVs, DS-RT still falls within the same range of RSS produced by the other 2 valves and control exceeding the threshold for platelet activation.

The Pursuit of Engineering the Ideal Heart Valve Replacement or Repair: A Special Issue of the Annals of Biomedical Engineering

Heart valve disease is a major component of heart disease and the significance of this disease is rising primarily due to increasing life expectancy as well as new percutaneous treatments becoming available to older patient populations who would otherwise only receive medical management. Treatments for severe heart valve disease vary from replacement with prosthetic heart valves or performing repair or implantation of palliative devices to improve valvular function. Unfortunately, current and past replacement and repair devices have not ‘‘solved’’ the problem due to continuing issues related to occurrence of complications (e.g. thromboembolism, need for pacemaker etc.) or compromise of valve function (e.g. structural deterioration of prosthetic leaflets, recurrence of mitral regurgitation after repair, valve leakage etc.) or the unintended introduction of a new problem (e.g. new issues resulting from the need for anticoagulation therapy). This explains the strong need and the current pursuit of engineering the ideal heart valve replacement or repair, which is the focus of this special edition. Two review articles are presented: (a) review by Dasi et al. on the mechanics of transcatheter aortic valve replacement (TAVR) which focuses on the current issues related to TAVR; and (b) the review by Espiritu et al. which focuses on trans-catheter mitral valve repair therapies. We have limited the reviews to transcatheter approaches alone for the aortic and mitral technologies given that numerous other review articles exist on the more traditional heart valve replacement and repair technologies. So what would be the ideal heart valve replacement or repair solution? While the best solution is prevention of valve disease, we will not be discussing preventative approaches in this edition because that would entail engineering in a different sense—understanding the pathophysiology of valve disease and engineering an intervention aimed to arrest or reverse disease progression. Here we focus on engineering new devices that will overcome the limitations of current replacement or repair devices. Two broad strategies emerge: (A) engineer a living tissue engineered heart valve that can replace the diseased heart valve and be immune to deterioration or disease processes or (B) engineer replacement or repair devices that are not biological in nature to overcome the limitations of current devices. Both strategies continue to be challenging because the mechanics of heart valves is inherently complex and unfortunately the heart valve engineering community does not yet fully understand the principles dictating how living tissue responds to mechanics or how a given valve design with novel synthetic materials would perform in vivo. Basic studies addressing this knowledge gap is progressing and a few articles are noteworthy along these efforts. The work presented by Kang et al. contributes to the body of knowledge that aims to 3D print cardiovascular soft tissues such as heart valves. Here they have elucidated the importance of stress mechanisms in the context of optimizing photo-encapsulation viability of heart valve cells for 3D printing applications. The article by Khalighi et al. aims to take advantage of regularities in the mitral valve structure to improve current mitral valve repair Lakshmi Prasad Dasi Jane Grande-Allen

Hemocompatibility of hyaluronan enhanced linear low density polyethylene for blood contacting applications

Despite their overall success, different blood-contacting medical devices such as heart valves, stents, and so forth, are still plagued with hemocompatibility issues which often result in the need for subsequent replacement and/or life-long anticoagulation therapy. Consequently, there is a significant interest in developing biomaterials that can address these issues. Polymeric-based materials have been proposed for use in many applications due to their ability to be finely tuned through manufacturing and surface modification to enhance hemocompatibility. In this study, we have developed a novel, hydrophilic biomaterial comprised of an interpenetrating polymer network (IPN) of hyaluronan (HA) and linear low density polyethylene (LLDPE). HA is a highly lubricous, anionic polysaccharide ubiquitously found in the human body. It is currently being investigated for a vast array of biomedical applications including cardiovascular therapies such as hydrogel-based regenerative cell therapies for myocardial infarction, HA-coated stents, and surface modifications of polyurethane and metals for use in blood-contacting implants. The aim of this study was to assess the in vitro thrombogenic response of the hydrophilic polymer surface, HA-LLDPE for future potential use as flexible heart valve leaflets. The results indicate that HA-LLDPE is non-toxic and reduces thromobogenicity as compared to LLDPE surfaces, asserting its feasibility for use as a blood-contacting biomaterial.