Matthew H Park1,2, Pearly K Pandya1,2, Yuanjia Zhu1,3, Danielle M Mullis1, Hanjay Wang1, Annabel M Imbrie-Moore1,2, Robert Wilkerson1, Mateo Marin-Cuartas1,4, Y Joseph Woo5,6. 1. Department of Cardiothoracic Surgery, Stanford University, Falk Cardiovascular Research Building CV-235, 300 Pasteur Drive, Stanford, CA, 94305-5407, USA. 2. Department of Mechanical Engineering, Stanford University, Stanford, CA, USA. 3. Department of Bioengineering, Stanford University, Stanford, CA, USA. 4. University Department of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany. 5. Department of Cardiothoracic Surgery, Stanford University, Falk Cardiovascular Research Building CV-235, 300 Pasteur Drive, Stanford, CA, 94305-5407, USA. joswoo@stanford.edu. 6. Department of Bioengineering, Stanford University, Stanford, CA, USA. joswoo@stanford.edu.
Abstract
PURPOSE: Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics. METHODS: Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n = 4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n = 18). RESULTS: The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p < 0.001), reduced effective orifice areas (p < 0.001), augmented transmitral mean gradients (p < 0.001), and increased leaflet stiffness (p = 0.025). CONCLUSION: This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.
PURPOSE: Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics. METHODS: Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n = 4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n = 18). RESULTS: The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p < 0.001), reduced effective orifice areas (p < 0.001), augmented transmitral mean gradients (p < 0.001), and increased leaflet stiffness (p = 0.025). CONCLUSION: This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.
Authors: Sean Coffey; Ross Roberts-Thomson; Alex Brown; Jonathan Carapetis; Mao Chen; Maurice Enriquez-Sarano; Liesl Zühlke; Bernard D Prendergast Journal: Nat Rev Cardiol Date: 2021-06-25 Impact factor: 32.419