None Declaration of conflict of interest
New Long Term Circulatory Support Technology and Treatment Strategies Stephen Westaby Oxford, UK
Cardiac Transplantation: Facts from the UNOS Database Median survival 12.2 years Waiting list mortality 8-10% One year mortality 15% Ten year mortality 58% More than 20% transplanted die in <3 years For the 58% who die <10 years, mean survival is 3.7 + 3.3 years Survival advantage only for UNOS Status I patients Kilic et al. Ann Thorac Surg 2012;93(3):699-704
Cardiac Transplantation: Facts from the UNOS Database Predictors of transplant longevity: Age <55 years, white race and no metabolic risk factors. Young donor age and short ischemic time. Predictors of poor transplant outcome: BMI > 30 kg/m 2, diabetes, renal impairment, need for preoperative ventilation. Borderline donor heart. Kilic et al. Ann Thorac Surg 2012;93(3):699-704
Survival with contemporary rotary blood pumps Jarvik Flowmaker PUMP 1 YEAR 2 YEAR LONGEST 87% 87% 7.5 years HeartMate II 85% 70% 7.2 years HeartWare HVAD 86% 78% 5.5 years INTERMACS Database 2012 80% 70% HeartMate XVE 2005 56% 33%
Preferred patient characteristics in regard to suitability for cardiac transplant or rotary blood pump Age INTERMACS profile UNOS Status Pulmonary vascular resistance BMI > 30kg/m 2 Type I Diabetes Renal Impairment (Creat >2.5 mg/dl) Right heart failure (CVP >20 mg Hg) Advanced vascular disease Previous malignancy Transplant <55 I I <2.5 Wood units Contraindication Contraindication Contraindication N/A Contraindication Contraindication LVAD <75 2-7 II <7.5 Wood units Acceptable Acceptable Acceptable Contraindication Acceptable Acceptable The treatments are complementary not competitive
Thoratec HeartMate II 281.3g (Pump body) 63 cc (Pump body) 7cc (Priming volume) Axial flow impeller with axial stator Radial flux gap motor in pump body Ceramic ball and cup bearings (both ends) 5L/min against 100 mm Hg at 12,000 rpm Survival to 7.2 years
HeartMate II Destination Therapy Trial Background Survival in Destination Therapy Trials 2 Initial HeartMate II Destination Therapy (DT) trial demonstrated significant improvements in outcomes compared to randomized patients with pulsatile LVADs 1 68% survival at 1 year 58% survival at 2 years Over 500 additional DT patients have been enrolled under continued access protocol (CAP) 1 Slaughter MS, Rogers JG, Milano CA et al: Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009 Dec 3;361(23):2241-51. 2 Fang JC: Rise of Machines Left Ventricular Assist Devices as Permanent Therapy for Advanced Heart Failure N Engl J Med. 2009 Dec 3;361(23):2282-84. Park, S, et al Circ Heart Fail 2012.
HeartMate II Destination Therapy Trial Continued Access Protocol Conclusions Trend towards improving survival Fewer deaths from hemorrhagic stroke What is the magnitude of absolute survival benefit with LVAD DT therapy? Significant reductions in adverse events: Hemorrhagic stroke >50% reduction Device related infections >35% reduction Sepsis >25% reduction Both QoL measures (KCCQ and MLWHF) demonstrated significant improvement over baseline values Source: Park SJ, AHA 2010
Percent Survival 100 HeartMate II Improving Destination Therapy Outcomes 90 80 70 60 50 40 30 20 10 0 Two Center (Advocate Christ-Duke) Results Late Experience June 2007 - April 2009 (n=55) Overall Experience March 2005 - April 2009 (n=93) Early experience March 2005 - May 2007 (n=38) (Included in Slaughter, Rogers, Milano et al NEJM 2009) Remaining at Risk: 55 43 12 93 64 30 38 21 18 0 6 12 18 24 Slaughter, Milano, Blue et al ISHLT 2010 85 + 5% 59 + 8% Months 70 + 8% 56 + 8%
Fully Implantable HeartMate II LVAS Game-Changing Program to Advance VAD Therapy and Patient Quality of Life WiTricity Partnership Single Implanted Component: Battery, Controller, Internal TETS Coil Initially configured with HeartMate II Proprietary resonant coils AC through power source coil induces a magnetic field Source coil s magnetic field induces current in the power capture coil, as well as a magnetic field Magnetic fields of the two coils couple tightly Enables high-efficiency, user-friendly wireless energy transfer across a distance Implanted components under development Focus on reduced size and reliability of electronics Advanced battery technology Custom cell technology tailored for implantable LVAD application Targeting untethered run times of ~3 hours; slow degradation for >3-year life Collaboration began in August 2010 Joint engineering team has demonstrated the ability to transfer power wirelessly to a HeartMate II LVAD Successfully started and ran the pump Currently working toward optimization of technology for incorporation into broader fully implantable HeartMate II program In development, not approved for clinical use
HeartMate III Ultra-Compact, Fully Magnetically Levitated VAD Secondary Flow Paths (pum gaps) Features Full support (10L / min) in ultra-compact size Magnetic levitation Artificial Pulse Small Pocket Controller Improved, modular driveline Intrathoracic placement Program Status Primary Flow Paths Design freeze on pump, motor, controller Design verification and pre-clinical testing underway Initiate CE Mark Clinical trials mid 2013 and US trial before the end of 2013 In development, not approved for clinical use
Jarvik 2000 Flowmaker 90g (Pump body) 25cc (Pump body) Survival to 7.5 years Axial flow impeller with axial stator Radial flux gap motor in pump body Ceramic (Silicon Carbide) conical bearing, hybrid contact hydrodynamic bearing
Jarvik Flowmaker with skull pedestal power delivery
MicroMed HeartAssist 5 95g (Pump body) Axial flow impeller with axial stator Radial flux gap motor in pump body Ceramic (Silicon Carbide) ball and cup bearing, hybrid contact hydrodynamic bearing
Berlin Heart INCOR 200g (Pump body) 60cc (Pump body volume) Axial flow impeller with axial stator Radial flux gap motor in pump body Active magnetic bearings Survival to 6.5 years
HeartWare HVAD 145g 45cc Pump body volume Survival to 5.5 years Radial flow impeller with spiral volute Axial flux gap motor in volute housing Radial passive magnetic bearing; also provides axial bias Hydrodynamic bearing on upper surface
Observed Survival HVAD Survival vs. Projected Survival FDA Circulatory Systems Device Panel, April 25, 2012 100 80 60 40 98% 83% 96% 71% 59 + 3% 94 + 2% 85 + 4% 45 + 3% HVAD- ADVANCE Trial SHFM Medical therapy 78 + 5% 20 0 HVAD Advance SHFM Medical Therapy HVAD- CAP BTT- Europe 29 + 2% 0 0.5 1 1.5 2 Years
Biventricular support with rotary blood pumps Problems - Ability to balance systemic and pulmonary blood flow - Pump inflow position in the right ventricle
Biventricular support with two HeartWare VADs
HeartWare MVAD Axial flow impeller with spiral volute Radial flux gap[ motor in inlet cannula Axial passive magnetic bearing
Terumo Duraheart 540g (Pump body) 196cc (pump body) Radial flow impeller with spiral volute Axial flux gap motor and magnetic levitation components in pump body Full active magnetic levitation with backup hydrodynamic bearing Survival to 4.5 years
Circulite Synergy 25g Pump body 1.9ml priming volume Mixed flow impeller with tangential radial outlet Radial flux gap motor in pump body Impeller uses ceramic ball and cup bearing with magnetic pre-load Motor is encapsulated within the pump body supported by a pair of ball race bearings at either end
Calon Cardio Technology MiniVad MiniVAD TM Radial impellor with radial motor Motor in inlet cannula to save space Impeller outside heart to improve efficiency and reduce blood damage Anatomical fit Pump Battery Pack & Console Strictly Confidential the contents of this document are the intellectual property of Calon Cardio-Technology Ltd and must not be communicated to any third parties without the written consent of Calon Cardio-Technology Ltd
Reduced Size x Motor parts (red) y Impeller parts (blue) y x Motor parts (red) Impeller parts (blue) Typical Axial Pump e.g. Thoratec Heartmate II Axial flow impeller, Radial flux gap motor Large size (two body cavities entered) Some blood damage issues Typical Radial Pump e.g. Heartware HVAD Radial flow impeller, Axial flux gap motor Large size outside of heart Some blood damage issues x y Motor parts (red) Impeller parts (blue) Calon MiniVAD Radial flow impeller, Radial flux gap motor VERY SMALL size outside of heart MINIMAL blood damage issues Strictly Confidential the contents of this document are the intellectual property of Calon Cardio-Technology Ltd and must not be communicated to any third parties without the written consent of Calon Cardio-Technology Ltd
The complete range of cardiac support Biventricular pacing, LVAD, defibrillator and stem cells
Myocardial Regeneration Therapy Cells and Assist Devices LVAD unloads the dilated LV and initially improves myocardial perfusion thus improving the environment for stem cell engraftment. Autologous bone marrow cells (CD105, CD34, CD133) exert predominantly paracrine effects to improve vascularity in hibernating myocardium and promote reverse remodelling. The effects are synergistic and improve native LV contractility. Improved contractility probably improves survival by reducing propensity for LV thrombus and thromboembolism.