RT Journal Article SR Electronic T1 Canary in the cardiac-valve coal mine: Flow velocity and inferred shear during prosthetic valve closure –predictors of blood damage and clotting JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.06.23.497372 DO 10.1101/2022.06.23.497372 A1 Lawrence N. Scotten A1 Rolland Siegel A1 David J. Blundon A1 Marcus-André Deutsch A1 Terence R. P. Martin A1 James W. Dutton A1 Ebrahim M. Kolahdouz A1 Boyce E. Griffith YR 2022 UL http://biorxiv.org/content/early/2022/09/22/2022.06.23.497372.abstract AB Objective To demonstrate a clear link between predicted blood shear forces during valve closure and thrombogenicity that explains the thrombogenic difference between tissue and mechanical valves and provides a practical metric to develop and refine prosthetic valve designs for reduced thrombogenicity.Methods Pulsatile and quasi-steady flow systems were used for testing. The instantaneous valve flow area was measured using analog opto-electronics with output calibrated to the projected dynamic valve area. Flow velocity during the open and closing periods was determined from the instantaneous volumetric flow rate divided by valve flow area. For the closed valve interval, data obtained from quasi-steady back pressure/flow tests was used. Performance ranked by the derived valvular flow velocity with maximum negative and positive closing flow velocities, indicts experimental evidence for potential clinical thrombogenicity. Clinical, prototype and control valves were tested.Results Establishment of a link between blood shear force and thrombogenicity led to optimization of a prototype mechanical bi-leaflet valve. The flow velocity metric was used to empirically design a 3-D printed model (BV3D) for softer valve closure dynamics which implicates reduced thrombogenic potential.Conclusions The relationship between leaflet geometry, flow velocity and predicted shear at valve closure illuminated an important source of prosthetic valve thrombogenicity. With an appreciation for this relationship and based on our experiment generated comparative data, we achieved optimization of valve prototypes with potential for reduced thrombogenicity.Graphical Abstract Static flow tests illustrate free jets of water passing through a closed mechanical valve (SJM). Investigations with pulsatile flow suggest similar fleeting jets arise near valve closure. Flow velocity determined in-vitro is evidence for shear forces that are predictive of blood cell damage and thrombogenic response. Red star is moment of valve closure.CENTRAL MESSAGE A derived laboratory metric for valve closing flow velocity offers a way to rank valve models for potential blood damage. These results provide new insight and a mechanistic explanation for prior clinical observations where aortic and mitral valve replacements differ in thrombogenic potential and anticoagulation requirement. The study suggests a path forward to design and evaluate novel mechanical valve models for future development. As multiple modifications to mechanical and bioprosthetic valves have not resolved chronic shortcomings related to thrombogenicity and durability, a new development avenue was required in order to eliminate thrombogenicity in the former and extend durability in the latter.PERSPECTIVE Prosthetic mechanical valve devices cause blood cell damage. Activation of the coagulation cascade is initiated by dynamic valve function. Design innovation focusing on valve closure behavior may reduce valve thrombogenic potential. Our study demonstrates that valve design can be optimized with emphasis on that phase.SIGNIFICANCE Attribution of valve leaflet geometry to occluder dynamic behavior and derived regional flow velocity may lead to the development of less thrombogenic valve replacements. Laboratory experiments support the supposition that valve regional flow velocity is associated with valve thrombogenic potential. This study compares three clinical valves and two experimental prototypes.Competing Interest StatementThe authors have declared no competing interest.