Fluid-Structure Interaction Models of Bioprosthetic Heart Valve Dynamics in an Experimental Pulse Duplicator.

Computer modeling and simulation is a powerful tool for assessing the performance of medical devices such as bioprosthetic heart valves (BHVs) that promises to accelerate device design and regulation. This study describes work to develop dynamic computer models of BHVs in the aortic test section of an experimental pulse-duplicator platform that is used in academia, industry, and regulatory agencies to assess BHV performance. These computational models are based on a hyperelastic finite element extension of the immersed boundary method for fluid-structure interaction (FSI). We focus on porcine tissue and bovine pericardial BHVs, which are commonly used in surgical valve replacement. We compare our numerical simulations to experimental data from two similar pulse duplicators, including a commercial ViVitro system and a custom platform related to the ViVitro pulse duplicator. Excellent agreement is demonstrated between the computational and experimental results for bulk flow rates, pressures, valve open areas, and the timing of valve opening and closure in conditions commonly used to assess BHV performance. In addition, reasonable agreement is demonstrated for quantitative measures of leaflet kinematics under these same conditions. This work represents a step towards the experimental validation of this FSI modeling platform for evaluating BHVs.

A Computational Study on Deformed Bioprosthetic Valve Geometries: Clinically Relevant Valve Performance Metrics.

Transcatheter aortic valves (TAV) are symmetrically designed, but they are often not deployed inside cylindrical conduits with circular cross-sectional areas. Many TAV patients have heavily calcified aortic valves, which often result in deformed prosthesis geometries after deployment. We investigated the effects of deformed valve annulus configurations on a surgical bioprosthetic valve as a model for TAV. We studied valve leaflet motions, stresses and strains, and analog hydrodynamic measures (using geometric methods), via finite element (FE) modeling. Two categories of annular deformations were created to approximate clinical observations: (1) noncircular annulus with valve area conserved, and (2) under-expansion (reduced area) compared to circular annulus. We found that under-expansion had more impact on increasing stenosis (with geometric orifice area metrics) than noncircularity, and that noncircularity had more impact on increasing regurgitation (with regurgitation orifice area metrics) than under-expansion. We found durability predictors (stress/strain) to be the highest in the commissure regions of noncircular configurations such as EllipMajor (noncircular and under-expansion areas). Other clinically relevant performance aspects such as leaflet kinematics and coaptation were also investigated with the noncircular configurations. This study provides a framework for choosing the most challenging TAV deformations for acute and long-term valve performance in the design and testing phase of device development.

In-Vitro Pulsatile Flow Testing of Prosthetic Heart Valves: A Round-Robin Study by the ISO Cardiac Valves Working Group.

PURPOSE: Hydrodynamic performance testing is one of the core in vitro assessments required by the ISO 5840 series of standards for all prosthetic heart valves. A round-robin study carried out in 2005 in accordance with ISO 5840:2005 revealed significant variabilities in prosthetic heart valve hydrodynamic performance measurements among the participating laboratories. In order to re-examine the inter-laboratory variability based on the "state-of-the-art" under ISO 5840-1 and 5840-2:2015, the ISO Cardiac Valve Working Groups decided in 2016 to repeat the round-robin study. METHODS: A total of 13 international laboratories participated in the study. The test valves were chosen to be the St. Jude Medical Masters Series mechanical valves (19 mm aortic, 25 mm aortic, 25 mm mitral, and 31 mm mitral), which were circulated among the laboratories. The testing was conducted according to a common test run sequence, with prespecified flow conditions. RESULTS: The study revealed improved, yet still significant variability among different laboratories as compared to the 2005 study. The coefficient of variation ranged from 7.7 to 21.6% for the effective orifice area, from 10.1 to 32.8% for the total regurgitant fraction, and from 14.7 to 45.5% for the mean transvalvular pressure gradient. CONCLUSIONS: The study revealed the ambiguities in the current versions of the ISO 5840 series of standards and the shortcomings of some participating laboratories. This information has allowed the ISO Working Group to incorporate additional clarifying language into the ISO 5840-1, -2, and -3 standards that are currently under revision to improve in vitro assessments. The results presented here can also be used by the testing laboratories to benchmark pulse duplicator systems and to train and certify testing personnel.

Impact of Clinically Relevant Elliptical Deformations on the Damage Patterns of Sagging and Stretched Leaflets in a Bioprosthetic Heart Valve.

After implantation of a transcatheter bioprosthetic heart valve its original circular circumference may become distorted, which can lead to changes in leaflet coaptation and leaflets that are stretched or sagging. This may lead to early structural deterioration of the valve as seen in some explanted transcatheter heart valves. Our in vitro study evaluates the effect of leaflet deformations seen in elliptical configurations on the damage patterns of the leaflets, with circular valve deformation as the control. Bovine pericardial tissue heart valves were subjected to accelerated wear testing under both circular (N = 2) and elliptical (N = 4) configurations. The elliptical configurations were created by placing the valve inside custom-made elliptical holders, which caused the leaflets to sag or stretch. The hydrodynamic performance of the valves was monitored and high resolution images were acquired to evaluate leaflet damage patterns over time. In the elliptically deformed valves, sagging leaflets experienced more damage from wear compared to stretched leaflets; the undistorted leaflets of the circular valves experienced the least leaflet damage. Free-edge thinning and tearing were the primary modes of damage in the sagging leaflets. Belly region thinning was seen in the undistorted and stretched leaflets. Leaflet and fabric tears at the commissures were seen in all valve configurations. Free-edge tearing and commissure tears were the leading cause of valve hydrodynamic incompetence. Our study shows that mechanical wear affects heart valve pericardial leaflets differently based on whether they are undistorted, stretched, or sagging in a valve configuration. Sagging leaflets are more likely to be subjected to free-edge tear than stretched or undistorted leaflets. Reducing leaflet stress at the free edge of non-circular valve configurations should be an important factor to consider in the design and/or deployment of transcatheter bioprosthetic heart valves to improve their long-term performance.

In-Vitro Pulsatile Flow Measurement in Prosthetic Heart Valves: An Inter-Laboratory Comparison.

BACKGROUND AND AIM OF STUDY: One of the first steps in qualifying a new prosthetic valve for eventual clinical use is preclinical flow performance testing in vitro. Such testing is typically performed in an in-vitro test system that simulates the pumping mechanics of the left ventricle of the heart, generally referred to as a pulse duplicator or duplicator. Historically, test results in these systems have varied from duplicator to duplicator. This collaborative effort between heart valve manufacturers and the Food and Drug Administration (FDA) was designed to evaluate the variability of the pulse duplicator test technology for pulsatile flow performance measurement in an interlaboratory round robin. METHODS: The participants jointly developed and followed a limited test protocol based on accepted methods outlined in the International Standards Organization 5840: Cardiovascular Implants - Cardiac Valve Prostheses, and in the FDA Replacement Heart Valve Guidance. One 25 mm valve, each of four basic designs, was circulated to test centers which included four manufacturers and two FDA duplicators. The pressure drop and regurgitation data were then collected and summarized by the FDA. RESULTS: Considerable variation was observed in hydrodynamic performance measures of pressure drop across the valve and back flow leakage through the valve among the different duplicators. Despite the variations seen in these measures, the results from all centers showed that the valves conformed to certain minimum performance criteria. CONCLUSIONS: Despite the fact that the valves would have been judged to have met Minimum Performance Requirements of effective orifice area and regurgitant fraction, as specified in the international standard, variations in measurements existed among duplicators. Valve manufacturers should use a reference valve of similar design in hydrodynamic performance testing to assess the individual measurement conditions in the duplicator.

Evaluation of one-way valves used in medical devices for prevention of cross-contamination.

BACKGROUND: One-way valves used in day use devices (used on multiple patients throughout a day without reprocessing between patients) are intended to reduce the potential for cross-contamination between patients resulting from the backflow of patient fluids. One-way valves are typically designed to withstand high levels of back pressure before failure; however, they may not be explicitly designed as a means of infection control as used in medical device applications. METHODS: Five different medical grade one-way valves were placed in low pressure configurations. After flushing in the intended direction of flow, bacteriophage, bacteria, or dye was placed patient side for 24 hours. The upstream device side of the valve was then evaluated for microbial growth or presence of visible dye. RESULTS: Leakage (ie, backflow) of the microorganisms occurred with a variety of one-way valve designs across a range of fluid properties tested. CONCLUSIONS: This study describes testing of the one-way valves (component-level testing) for the potential of cross-contamination. Although day use medical device systems may use numerous other factors to prevent patient cross-contamination, this work demonstrates that one-way valves themselves may not prevent leakage of contaminated fluid if the fluid is able to reach the upstream side of the one-way valve.

A Parametric Computational Study of the Impact of Non-circular Configurations on Bioprosthetic Heart Valve Leaflet Deformations and Stresses: Possible Implications for Transcatheter Heart Valves.

Although generally manufactured as circular devices with symmetric leaflets, transcatheter heart valves can become non-circular post-implantation, the impact of which on the long-term durability of the device is unclear. We investigated the effects of five non-circular (EllipMajor, EllipMinor, D-Shape, TriVertex, TriSides) annular configurations on valve leaflet stresses and valve leaflet deformations through finite element analysis. The highest in-plane principal stresses and strains were observed under an elliptical configuration with an aspect ratio of 1.25 where one of the commissures was on the minor axis of the ellipse. In this elliptical configuration (EllipMinor), the maximum principal stress increased 218% and the maximum principal strain increased 80% as compared with those in the circular configuration, and occurred along the free edge of the leaflet whose commissures were not on the minor axis (i.e., the "stretched" leaflet). The D-Shape configuration was similar to this elliptical configuration, with the degree to which the leaflets were stretched or sagging being less than the EllipMinor configuration. The TriVertex and TriSides configurations had similar leaflet deformation patterns in all three leaflets and similar to the Circular configuration. In the D-Shape, TriVertex, and TriSides configurations, the maximum principal stress was located near the commissures similar to the Circular configuration. In the EllipMinor and EllipMajor configurations, the maximum principal stress occurred near the center of the free edge of the "stretched" leaflets. These results further affirm recommendations by the International Standards Organization (ISO) that pre-clinical testing should consider non-circular configurations for transcatheter valve durability testing.

A novel study of mechanical heart valve cavitation in a pressurized pulsatile duplicator.

Submission of data regarding the cavitation potential of a mechanical heart valve is recommended by the U.S. Food and Drug Administration in the device-review process. An acoustic method has long been proposed for cavitation detection. However, the question as to whether such a method can differentiate the cavitation noise from the mechanical closing sound has not been sufficiently addressed. In this study, cavitation near a Medtronic Hall tilting disc valve was investigated in a pressurized pulsatile duplicator. The purpose of pressurizing the testing chambers was to prevent cavitation under a normally cavitating loading condition to isolate the mechanical closing sound. By comparing the sound signals before and after pressurization, some noticeable differences were found between them. In the time domain, the intensity of the sound under a cavitating condition was much higher. In the frequency domain, the energy distribution of a sound signal was distinctively different depending on whether cavitation occurred or not. The valve closing sound had a large amount of energy in the low-frequency range (less than about 25 kHz). When cavitation took place, the sound energy shifted toward the high-frequency range (from 25 to 500 kHz).

On the closing sounds of a mechanical heart valve.

In the 1994 Replacement Heart Valve Guidance of the U.S. Food and Drug Administration (FDA), in-vitro testing is required to evaluate the potential for cavitation damage of a mechanical heart valve (MHV). To fulfill this requirement, the stroboscopic high-speed imaging method is commonly used to visualize cavitation bubbles at the instant of valve closure. The procedure is expensive; it is also limited because not every cavitation event is detected, thus leaving the possibility of missing the whole cavitation process. As an alternative, some researchers have suggested an acoustic cavitation-detection method, based on the observation that cavitation noise has a broadband spectrum. In practice, however, it is difficult to differentiate between cavitation noise and the valve closing sound, which may also contain high-frequency components. In the present study, the frequency characteristics of the closing sound in air of a Björk-Shiley Convexo-Concave (BSCC) valve are investigated. The occluder closing speed is used as a control parameter, which is measured via a laser sweeping technique. It is found that for the BSCC valve tested, the distribution of the sound energy over its frequency domain changes at different valve closing speeds, but the cut-off frequency remains unchanged at 123.32 +/- 6.12 kHz. The resonant frequencies of the occluder are also identified from the valve closing sound.

Effects of valve characteristics on the accuracy of the Bernoulli equation: a survey of data submitted to the U.S. FDA.

BACKGROUND AND AIM OF THE STUDY: In 1988, valve manufacturers petitioned the U. S. Food & Drug Administration (FDA) to replace catheter with Doppler ultrasound measurements of pressure gradient (delta P) in clinical studies. Manufactures agreed to submit bench data validating the Bernoulli equation used to calculate delta P = delta P = K(Vd2 - Vp2), where K = constant, Vd = distal Doppler velocity, and Vp = proximal Doppler velocity. Previous studies suggest that K may vary from the idealized 4.0, which could lead to incorrect valve assessment and clinical errors. METHODS: Variation in K-values in marketing application data submitted to the FDA was assessed. Pulse duplicator data included four bileaflet valves, two stented bioprostheses, and seven stentless bioprostheses, sized from 19 to 33 mm. Effects of valve type, valve size, blood-mimicking fluid used, and distal pressure tap position (DPTP) were evaluated via an analysis of variance. RESULTS: K-values varied from 2.50 to 7.40 (n = 90). K was found to be dependent on valve type (p < 0.0001), blood-mimicking fluid (p < 0.0001) and DPTP (p < 0.0001), but not valve size. At DPTP = 30 mm, K = 3.43 +/- 0.56, 5.15 +/- 0.81, and 4.81 +/- 1.02, for bileaflet, stented and stentless valves, respectively. K averaged 10% less using the 100-mm DPTP, due to pressure recovery. Variations due to blood-mimicking fluid were likely related to the fluid density. CONCLUSION: Variations due to DPTP and fluid used are consistent with physical mechanisms of pressure recovery and fluid density. Results from previous studies have suggested that effects of valve type on K are also real. The magnitude of these effects appeared to be +/- 25%. Extrapolation to patients is difficult, but clinicians should be aware that Doppler measurements may vary by similar amounts. Doppler pressure gradients should be interpreted qualitatively and moderated by other diagnostic measures of valve performance.