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bioRxiv · 10.1101/2022.06.23.497372

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

Scotten, L. N.·Siegel, R.·Blundon, D. J.·Deutsch, M.-A.·Martin, T. R. P.·Dutton, J. W.·Kolahdouz, E. M.·Griffith, B. E.
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Abstract

ObjectiveTo 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. MethodsPulsatile and quasi-steady flow systems were used for testing. The time-variation of projected open area (POA) was measured using analog opto-electronics calibrated to projected reference orifice areas. Flow velocity determined over the cardiac cycle equates to instantaneous volumetric flow rate divided by POA. For the closed valve interval, data from quasi-steady back pressure/flow tests was obtained. Performance ranked by derived maximum negative and positive closing flow velocities, evidence potential clinical thrombogenicity via inferred velocity gradients (shear). Clinical, prototype and control valves were tested. ResultsBlood shear and clot potential from multiple test datasets guided empirical optimization and comparison of valve designs. Assessment of a 3-D printed prototype valve design (BV3D) purposed for early soft closure demonstrates potential for reduced thrombogenic potential. ConclusionsThe 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. Competing InterestsNone declared. Financial DisclosureThis research has been done on a pro bono basis by all authors. Graphical AbstractVisualization of water jetting through closed mechanical heart valve under steady flow. Under pulsatile conditions, similar jet patterns near valve closure and leaflet rebound are likely. Dynamic metrics for several valves assessed in vitro are important in prediction of comparable blood cell damage and potential life-threatening thrombotic outcomes. Red star indicates moment of valve closure. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/497372v11_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@95677forg.highwire.dtl.DTLVardef@bdc94dorg.highwire.dtl.DTLVardef@1eaf113org.highwire.dtl.DTLVardef@1792ade_HPS_FORMAT_FIGEXP M_FIG C_FIG CENTRAL MESSAGEA 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 to lead to eliminate thrombogenicity in the former and extend durability in the latter. PERSPECTIVEProsthetic 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 empirically optimized with emphasis on that phase. SIGNIFICANCEEmphasis on open valve performance has encouraged a long-standing bias while under appreciation of the closing phase vital to identification of potential thrombogenic complications persist. Our multiple data sets are useful in challenging this bias. Dynamic motion(s) of mechanical valves and derived regional flow velocity are impacted by valve geometry. Focus on valve closure dynamics may lead to the development of potentially less thrombogenic prototype valves. 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.

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Scotten, L. N., Siegel, R., Blundon, D. J., Deutsch, M.-A., Martin, T. R. P., Dutton, J. W., Kolahdouz, E. M., Griffith, B. E.. 2022-06-26. Canary in the cardiac-valve coal mine: Flow velocity and inferred shear during prosthetic valve closure --predictors of blood damage and clotting. https://doi.org/10.1101/2022.06.23.497372

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