Preclinical evidence

Exhaustive experimental, numerical and animal testing have been performed on previous versions of the LTV heart valve (made of Delrin® polymer and carbon materials), in accordance with FDA and International ISO Standards(*) confirming the safety and effectiveness of the valve. 

Testing is in progress on the final version of the valve made of a new high-performance polymer, whose intrinsic properties are intended to outperform older materials.


In-vitro testing

The design of the LTV heart valve has been validated and optimized by means of state-of-the-art experimental and numerical testing(*)

  • Hydrodynamic performance tests.  Read more...
    • Selection of tests performed:
    • Flow patterns, velocity profiles and shear stresses in steady and pulsatile flow via Computational Fluid Dynamics (CFD), Digital Particle Image Velocimetry (DPIV), and Laser Doppler Anemometry (LDA).
    • Pressure drop and leakage volume in steady flow.
    • Pressure drop, regurgitant volume and energy loss in pulsatile flow.
    • Flow patterns in steady flow via flow-visualization methods (washout experiments for flow separation detection).
    • Cavitation threshold.
    • Opening and closing kinematics via Dynamic Projected valve area and high-speed video recording and enlarged model studies.
    • Selection of results obtained
    • Similar flow structure and opening and closing kinematics as tissue valves (drastically different from current mechanical valves).
    • No pathological micro bubbles cerebral emboli at closure (HITS), no pathological fluid forces and turbulences (cf. echo-doppler comparative tests), like tissue valves and unlike current mechanical valves.
    • No permanent stagnation areas could be detected by CFD.
    • Higher cavitation threshold than the ones obtained with two references bileaflet mechanical heart, indicating a lower risk for potential material and blood cell damage.
    • Optimal washout behavior.
    • DPIV studies show well-defined core flow with small wakes behind the leaflet and washout of the sinuses of Valsalva during valve closure and opening.
  • Structural performance tests.  Read more...
    • Finite Element Analysis and Burst Testing:  the LTV heart valve proved to more robust than reference mechanical valves.
  • Durability and wear tests.  Read more...
    • Accelerated wear testing (according to ISO 5840) has been performed on previous versions of the LTV valve without structural failure or valve dysfunction:
    • During 280 million cycles (equivalent to nearly eight years) with the first prototypes with leaflets made of Delrin® polymer, a material with a satisfactory performance history in previous mechanical heart valves40, 41. Note that Delrin® polymer is less resistant to wear and fatigue than the new high-performance polymer used the current model FURTIVA® valve.
    • During 400 million cycles (equivalent to more than 11 years) with valves made of carbon material.


From 1980 to 2009, comparative in-vitro testing has been performed by independent institutes
(*), including:

    1. Helmholtz-Institute (Aachem, Germany)
    2. California Institute of Technology, CALTECH (Pasadena, California, U.S.A.)
    3. Simulog (Toulouse, France)
    4. Vivitro Systems, Inc. (Victoria, Canada)

Further tests are in progress on the final version of the valve by a number of these institutes, as well as with other independent institutes, including:

    1. École Polytechnique Fédérale de Lausanne (EPFL)
    2. Swiss Federal Institute of Technology, Zürich (ETH)
    3. Bern University, Artorg Center Biomedical Engineering Research (Artorg)

 

“The combined use of state-of-the-art engineering techniques has resulted
in a new mechanical tri-leaflet valve with superior hydraulic and kinematic properties.”
Prof. H. Reul, Helmholtz-Institute,  Aachem, Germany

 


Animal testing

More than 100 successful long-term (up to 1.5 years) anticoagulant-free animal implants have been performed with no obstructive thrombosis(*).

  • 60+ calves
    Dr. O.H. Frazier, Texas Heart Institute, Houston
    Read more...

    • Design and performance testing.
    • Implants in mitral position of valves made with Delrin® polymer leaflets during  5 to 9 months37.
    • Comparative implants in aortic and mitral positions (GLP) during 6 to 18 months42, 43, 44.
      Monthly Transthoracic Echo-Doppler + regular blood tests
      Explanted valves clean with no signs of local thrombosis.

    • “Prototype trileaflet valves performed safely and effectively in the mitral position in calves, even without long-term anticoagulation.42
  • 26 sheep
    Prof. Richard W. Bianco, University of Minnesota
    Read more...

    • Preclinical evaluation of safety and efficacy.
    • Comparative implants in aortic and mitral positions during 150 days and 365 days.
      Angiography, echocardiography, and pathology were performed to assess valve performance.

      “Valve has demonstrated preclinical safety and should proceed to clinical.”
      38
  • 9 sheep 
    Prof. Bart Meuris, W. Flameng, KU Leuven, Belgium
    Read more

    • Tests performed on improved versions of the valve (T2b and T2c).
    • Implants in pulmonary position in juvenile sheep, in comparison with a bi-leaflet valvea.
      Valve explanted after 10 weeks: results suggest a significantly longer survival rate for the Triflo valves, compared to standard bi-leaflet valves.
  • 1 sheep and 2 calves
    Prof. Willem Flameng, KU Leuven, Belgium and Dr. O.H. Frazier, Texas Heart Institute
    Read more

    • Tests performed on the final design of the valve.
      1 sheep, Flameng’s pulmonary test, 21 weeks: no clot deposits (unlike standard bi-leaflet valves, which failed before 12 weeks by clot deposits in the hinges and valve dysfunction).
      2 calves, Dr. O.H. Frazier, 26 weeks: valves were “clean as a whistle at explants with outstanding pathological results.

 

“Overall, the Triflo valve appeared to more closely emulate the hemodynamic properties
of the native tissue valve than the traditional bi-leaflet design. Hence, the tri-leaflet design
may offer the function of a tissue valve while retaining the durability of the mechanical valve.” 38
Prof. Richard W. Bianco, University of Minnesota

 

 


(*) Full data on file at Novostia SA