Violin plot data: A concerto of crucial information on valve thrombogenicity categorized in vitro by valve motion and inferred flow velocity

Abstract

Objectives: We hypothesize that prosthetic valve thrombogenic potential may be inferred by valve regional flow velocity. This metric was used to compare two clinical valves and two experimental prototypes. Methods: Four our clinical and experimental prototype valve models were tested in aortic and mitral sites under pulsatile circulation in a pulse duplicator. An optical approach measuring projected dynamic valve area to gauge valve motion was implemented. Pulsatile pressures and flow rates were measured by conventional techniques and a quasi-steady flow tester was used to measure valve leakage. Regurgitant flow velocity was derived using time-dependent volumetric flow rate / projected dynamic valve area. Since flow velocity and fluid shear force are related through flow velocity gradient, thrombogenic potential for valves that achieve near closure during the forward flow deceleration phase were determined as regurgitant flow velocities relative to the control mechanical valve regurgitant flow velocity of -126 m/s. Analysis of the flow velocity data made use of Vioplot R* and VISIO software packages to provide split violin plots that represent probability of recurrence of data. Results: Thrombogenic potential was made dimensionless and ranged between -0.45 and +1.0. Negative thrombogenic potentials arise when transient rebound of valve occluder is accompanied by water-hammer phenomena. Positive thrombogenic potentials occur during decelerating forward flow. Bioprostheses had lowest thrombogenic potential transient of 0.15. A mock-transcatheter aortic valve replacement incorporating by design a trivial paravalvular leak (~1.35 ml/s) demonstrated a high transient thrombogenic potential of 0.95. Conclusions: Our data reveals distinct thrombogenic potential profile differences between valve models. If our study methods are verifiable, the design of future valves may utilize currently available experimental tools to produce advanced devices with significantly reduced thrombogenic potential.

Canary in the cardiac-valve coal mine. Flow velocity and inferred shear during prosthetic valve closure –predictors of blood damage and clotting

“…Readers will note that in prior publications, closing flow velocities in excess of those observed in this study were reported [5][6][7][8][9][10]. Previous records with excessive closing flow velocities have been rectified in this report by re-analysis of the historical experiment test datasets imported into revised EXCEL templates.…”

“…Over time, progressive adaptations to the pulse duplicator apparatus have been reported [1][2][3][4][5][6][7][8][9][10][11][12]. This included the optical measurement of valve kinematics and in silico evaluations [3][4][5][6][7][8][9][10][11][12][13][14][15].…”

“…Study outcomes (previous and present reports) [3][4][5][6][7][8][9][10]: 1. High amplitude valve closing flow velocities may result in supra-physiologic shear forces originating in small intra-and para-valvular leak gaps and which become mechanistic initiators of the clotting cascade.…”

“…Over time, progressive adaptations to the pulse duplicator apparatus have been reported [1][2][3][4][5][6][7][8][9][10][11][12]. This included the optical measurement of valve kinematics and in silico evaluations [3][4][5][6][7][8][9][10][11][12][13][14][15]. Aforementioned conditions and settings used in this study are applicable to Figure 1 and are related to fluid-structure interaction (FSI) studies and associated boundary conditions [11][12][13][14][15].…”

“…The addition of this subsystem redirected our interest in heart valve dynamics to the closure phase and associated supra-physiologic backflow fluid velocities. Driven by ongoing curiosity and armed with new data from Leonardo, we reported our findings through a series of preprints and publications [4][5][6][7][8][9][10][11][12]. In a recent broader application of our investigative technology, results from in silico computational modeling and in vitro experimental studies provided validation of the characteristics of bioprosthetic valve leaflet flutter along with invited peer commentary [11][12][13][14][15].…”