1、Practical and Engineering Considerations in Catheter-based Aortic Valve Development,Robert F. Wilson, M.D. University of Minnesota,Percutaneous Valve Design Requirements,Deliverability Delivering the valve to the valve orifice Deployability Accurately deploying the valve in the valve orifice Stickab
2、ility Designing the valve to adhere to the valve orifice Functionality Valve functions as a one-way valve for the orifice Durability Valve retains function and position for the desired lifetime,Delivery Size (!),Delivery system diameter determines delivery options Normal adult human vascular dimensi
3、ons: Femoral artery averages 4.5-7.6 mm in diameter (14-24 Fr) Femoral vein averages 10 mm in diameter (31 F) 5-7% of patients with a 9.5 Fr IABP develop limb ischemia,OLIVE et al: Med. Sci. Sports Exerc., 35:901-907, 2003. Ohman et al: Circulation. 90(2):792-9, 1994 Pfieffer et al: J Cardiovasc Sur
4、g 2005;46:55,Packing size: “putting 5 gm in a 2 gm bag”,A 21 mm cuff has a circumference of 66 mm A 19 mm valve diameter as a circumference of 60 mm,+,20 F,4.7 mm,15 mm,15 F,Available Internal CSA Based on Guide Catheter Outer Diameter,Delivery catheter internal CSA (assuming wall thickness = 0.28 m
5、m) 10 F 6.60 12 F 9.73 14 F 13.59 16 F 18.09 18 F 23.24 20 F 29.03 22 F 35.43 24 F 42.31,CSA= cross-sectional area,iCSA (mm2),Available valve material,Stent thicknesses range from: 0.002 to 0.010” Pericardial thicknesses range from: Bovine 0.012-0.014” Porcine 0.007-0.008” Equine 0.006-0.007” SIS 0.
6、002-0.003”,Packed CSA for Valve Tissue,Porcine pericardium,Bovine pericardium,Equine pericardium,SIS,Packed CSA for Valve Cuff or Stent,Nitinol,Stainless steel,Packed valve CSA v. Delivery Catheter CSA,Valve CSA (packed),Cuff CSA (packed),CSA (mm2),Big Delivery Catheters = Big Problems,Many percutan
7、eous aortic valves under development require delivery catheters 20 Fr. This necessitates: a transvenous-trans-septal approach or a high level of peripheral vascular complications,Approaches to reducing delivery size,Find thinner valve leaflet material Equine pericardium SIS (intestinal mucosa) Nano
8、skeleton with “seeded” valve tissue “Extrude” the valve,HLT Valve: 15.5 Fr Delivery System,Percutaneous Valve Design Requirements,Deliverability Delivering the valve through the valve orifice Deployability Accurately deploying the valve in the valve orifice Stickability Designing the valve to adhere
9、 to the valve orifice Functionality Valve functions as a one-way valve for the orifice Durability Valve retains function and position for the desired lifetime,Anatomy of the Aortic Valve the crowded neighborhood,The aortic valve is a reflection of the aorta No true annulus The valve margins abut eac
10、h cardiac chamber and the pericardium,Anatomy of the Aortic Valve the crowded neighborhood,The right cusp is connected to the interventricular septum The left cusp is in continuity with the anterior leaflet of the mitral valve,anterior mitral leaflet,http:/ Interference,Mitral anterior leaflet Inter
11、ference Abrasion Wear surface Coronary interference Prosthetic valve Calium nodules,anterior mitral leaflet,Coronary obstruction,richmond/heart.html,Percutaneous Valve Design Requirements,Deliverability Delivering the valve through the valve orifice Deployability Accurately deploying the valve in th
12、e valve orifice Stickability Designing the valve to adhere to the valve orifice Functionality Valve functions as a one-way valve for the orifice Durability Valve retains function and position for the desired lifetime,The Major Displacement Load is During Diastole,At valve closure, the load on the va
13、lve is:,Aortic pressure- LV pressure,Calculation of maximal valve load,Good design incorporates a 3X safety standard 3.6 lb 1.6 kg,Assume: Maximal blood pressure at valve closure = 155 mmHgLV pressure at valve closure = 15 mmHgMaximal valve load= 140 mmHg,140 mmHg = 2.7 psi18.6 kPa,19 mm diameter va
14、lve CSA = 0.44 in22.82 cm2,Valve load = 2.7 psi X 0.44 in2 = 1.19 lb0.54 kg,Valve obstruction leads to massive forward force on the valve,Good design incorporates a 3X safety standard 3.6 lb 1.6 kg,280 mmHg = 5.4 psi37.2 kPa,19 mm diameter valve CSA = 0.44 in22.82 cm2,Valve load = 2.7 psi X 0.44 in2
15、 = 2.4 lb1.1 kg,Testing “Stickability”,We need a standardized pull test and standard Present valves should aim for a pull test of at least 1.6 kg (3.6 lbs) retrograde 3.2 kg (7 lb) forward,Pull test,Percutaneous Valve Design Requirements,Deliverability Delivering the valve through the valve orifice
16、Deployability Accurately deploying the valve in the valve orifice Stickability Designing the valve to adhere to the valve orifice Functionality Valve functions as a one-way valve for the orifice Durability Valve retains function and position for the desired lifetime,Parameters of Valve Function,Adeq
17、uate effective orifice area (EOA) EOA geometric area Minimal aortic insuficiency Minimal turbulance Turbulance leads to hemolysis and thrombosis,What is the minimal EOA? patient prosthesis mismatch,Small valves are associated with reduced functional capacity EOA 0.85 cm2/m2 In native aortic valve st
18、enosis, hypertrophy begins at: EOA 0.8 cm2/m2,The minimal EOA should be 0.85 cm2/m2 For an average North American: 1.5 cm2,Blais et al: Circulation. 2003;108:983 Pibarot et al : J Heart Valve Dis. 1998; 7:211,0.65 cm2/m2,0.85 cm2/m2,The geometry of stenotic aortic valves varies: the new valve must f
19、it the orifice,Tricuspid valves open to an irregular shape with commissural fusion points Bicuspid valves have a slit like orifice Calcification at the valve margin can impinge of a prosthetic valve,Images from: 43855a_app4.gif,Aortic insufficiency due to valve-orifice mismatch,Aortic insufficiency
20、 due to valve-orifice mismatch,Non-conforming stent valves lead to perivalvular leak Tissue skirts or valve wraps reduce leak Conforming valves may reduce leak,Blood Flow Through the Aortic Valve,Blood is ejected through the valve such that it is aimed at the tubular portion of the aorta Minimal tur
21、bulence Fairly small angle of opening Less valve flexion and wear Number of methods for measuring flow profile Laser anemometry Thin film anemometry Particle image velocimetry CFD calculations Flow profiling important for assessing prosthetic valves Turbulence correlates with thrombosis High shear s
22、tress correlates with hemolysis,Percutaneous Valve Design Requirements,Deliverability Delivering the valve through the valve orifice Deployability Accurately deploying the valve in the valve orifice Stickability Designing the valve to adhere to the valve orifice Functionality Valve functions as a on
23、e-way valve for the orifice Durability Valve retains function and position for the desired lifetime,Biological materials used for heart valves,Pericardium Bovine Porcine Equine SIS Animal valves Bovine jugular Porcine aortic,Stent or Cuff Materials,Stainless steel Nitinol Polymer,Nitinol,Superelasti
24、c metal (NiTi)Excellent fatigue resistance from repetitive strain NiTi stress/strain characteristics and fatigue are difficult to characterize due to variances in alloy composition and porosityCorrosion properties and biocompatibility dependent on surface characteristics Porous surface leads to more
25、 fibrosis Surface oxidation can greatly reduce fatigue resistance Coating or electro-polishing improve corrosion resistance,Heintz et al: Journal of Endovascular Therapy: Vol. 8, No. 3, pp. 248253.,Valve Durability- In-Vitro Testing,Each normal valve cycles about 100,000 times a day 36 million times
26、 a year 720 million times in 20 years 2.9 billion times in a lifetime (2.6 in men) Accelerated prosthetic valve wear testing is required to detect fatigue failures. 400-600 million cycles Usually tested in a high speed cycler using glycerol fluid 600 million cycles requires 10-12 months,Animal Model
27、s of Aortic Stenosis,Clinical Testing,FDA requirements for new surgical valves include: Hemodynamic characterization Effective orifice area (EOA) Flow profile analysis Durability testing for 600 million cycles Structural analysis Animal implant testing 6-12 animal implants for 6-12 months Accelerate
28、d calcification testing (tissue valves) Calf model Biocompatibility testing Clinical study demonstrating: 400 patient years per position (mitral, aortic, etc.) Results showing non-inferiority to approved valve,Evolution of Approvals,No-option patients,Surgical candidates,Minimally invasive surgical
29、approach,General percutaneous approval,Minimally invasive surgical approval,2003,No-option Patients,How many are there? Euro Heart Study 33% of patients 75 years old with severe aortic valve stenosis were not operated. 16% mortality at 1 year.,Operated (%),LV Ejection fraction (%),Comparison of Percutaneous Aortic Valves,Is this a replay of early surgical valve development?,
