5(2012.5.25) () () () 189 320 667 1,193 2,174 2,728 3,151 3,381 4,021 4,216 4,251 4,425 4,484 4,452 4,314 4,245 3,943 3,700 3,571 3,528 3,408 3,367 3,294 3,370 3,406 3,389 3,353 4500 4000 3500 3000 2500 2000 1500 1000 500 0 CyA BTT 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 ISHLT J Heart Lung Transplant. 2010; 29: 1083-1141 1982 1983 Number of Transplants Jarvik 7 1 st patient (1982) VAD(1980) Survived 112 days
1.0 0.8 0.6 0.4 0.2 0.0 VAD (Nipro VAD54 vs VAD: 20) 4 95 169 257 341 0 365 730 1095 1460 () ADULT HEART TRANSPLANTATION Kaplan-Meier Survival by VAD usage (Transplants: 1/1999-6/2009) Survival (%) 100 90 80 70 60 50 Conditional on Survival to 6 Months No pair-wise comparisons are statistically significant at p < 0.05 Pulsatile flow (N=2,793) No LVAD / No Inotropes (N=7,089) 0 1 2 3 4 5 6 7 8 9 ISHLT 2011 Years J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 6 Continuous flow (N=776) No LVAD / Inotropes (N=7,469) Number of VAD Therapy in Univ. of Tokyo Hosp. Clinical trial ilvad Approval ilvad 20 18 16 14 12 Jarvik2000 DuraHeart 2012.1.20 10 8 6 4 2 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 EVAHEART HeartMate XVE Paracorporeal VAD Nipro (Implantable Rotary VAD: 20pts, Nipro VAD54 pts)
Novacor carried serious problems in Insurance Reimbursement Rule Novacor BTT Device Cardiovascular Med-Surg 2005;7(2):279-283 LVAD :(H17,18) : (H19) LVAD(H20) (H21) (H22 ) : VAD(H21, ) (H23) (H21) J-MACS(H22, PMDA) EVAHEART, DuraHeart () (28) DuraHeart EVAHEART2010128 ISO 14708-5 DuraHeart EVAHEART 15 24
GLP GCP QMS/GQP GPSP/GVP GLP= GCP= QMS= GQP= GPSP= GVP= WG WG WG WG WG WG WG H1 A B C D E F G H
TAH/VAD 2007 80% reliability, 60% confidence level 6 80% reliability, 80% confidence level 2 6 60 8 90 WG TAH/VAD (EMC) in vitro in vivo 10 11 ANNEX A ANNEX B ANNEX C Yamane T, Kyo S, Matsuda H, et al.: Japanese Guidance for Ventricular Assist Devices/Total Artificial Hearts, Artificial Organs, Vol.34, No.9, 2010 NEDO VAD 268 VAD 63
NEDO VAD 8908on going TAH/VAD 0404002 H20.4.4) Feasibility study 5 Pivotal study 15 Feasibility study 3 Pivotal study 6 DT 12 BTT 1 DT 24 DT WG DuraHeart & EVAHEART 2004 DuraHeart 33 2005 EVAHEART 18 2007.6 2007.5 2008.4 2008 DuraHeart 6 2009.1 EVAHEART 2009.9 DuraHeart 2009 2010 2010 2010.1 ISO14708-5 Circulastory Support Devices 2010.11.19 1524 2010.12.08 4 20083 1. 2. J-MACS 3. 4. ( ) (1) (2)
BSA NYHA:- D ( ) ACEARB IABP 65( 65) stage D, NYHA QOL QOL BSA NYHA:- D ( ) ACEARB IABP 65( 65) stage D, NYHA QOL QOL J-MACS LVAD LVAD(23) EVAHEART 18 Jarvik 2000 6 DuraHeart 6 6 36
(Kaplan-Meyer) Kaplan-Meier 1.8 (n=11) 5 2298 7.6.4.2 0 (719=53%) (n=36) 6 + (27=64%) 7 VAD 0 500 1000 1500 2000 2500 Japanese registry for Mechanically Assisted Circulatory SupportJ-MACS 61 DC Data Base VAD EVAHEART 32 DuraHeart LVAD 28 60 (2012.4.1) BVAD BVAD 31 1 26 1 1 57( 95%) 1(1.7%) 1(1.7%) 1(1.7%)
New Strategy of VAD therapy Bridge to transplantation (BTT) Bridge to recovery (BTR) Destination Therapy (DT) New Strategy of VAD therapy Bridge to transplantation (BTT) Bridge to recovery (BTR) Destination Therapy (DT) Bridge to decision implantable VAD Bridge to bridge implantable VAD Bridge to therapy BTR Bridge to candidacy BTT NIPRO VADBridge to Bridge LVAD:534 BTR=Bridge to Therapy -blocker, ACEI, ARB) (MVPDor) () BTR us markets for ventricular assist devices 2008; Millennium Research Group, Inc.
(2005.8.27) (2007.12.14) Gojo S, Kyo S, Nishimura S et al. Cardiac resurrection after bone-marrow-derived mononuclear cell transplantation during left ventricular assist device support. Ann Thorac Surg 2007:83: 661-662. 227? (3050/) VAD VAD LVAD : destination therapy VAD LVAD LVAD
LVAD : destination therapy VAD LVAD LVAD % Survival 100 90 80 70 60 50 40 30 20 10 Implant Dates: June 23, 2006 March 31, 2009 Device Strategy at Implant Destination = 120, deaths = 49 BTT = 1184, deaths = 213 p=.01 Event: Death (censored at transplant or recovery) 0 0 3 6 9 12 15 18 21 24 Months after Device Implant LVAD : destination therapy VAD LVAD LVAD
BTT(?) BTT ECMO (<1) VAD() Excor (Berlin Heart) Clinical trial : Berlin Heart Excor 10ml 25ml 30ml 50ml 60ml 10ml Jarvik Heart Inc. PumpKIN Preclinical Program NCVC, Mitsubishi Pump NEDO Project (2010-2015) LVAD : HVAD (HeartWare):145g destination therapy VAD DuraHeart (Terumo) DuraHeart2 (Prototype) EVAHEART LVAD 110g LVAD
(20) LVAD LVAD : destination therapy 10 82 VAD 53 LVAD NCVC() LVAD Need of Implantable LVAD Center (LVAD) + 23 24 21 LVAD (/) CRT 5 (100/)
3,000 2,500 VAD (2011.1.13 ) 3(2012.3.31, ) VAD 2013. New Hospital Open 2,000 1,500 1,000 500 0 2007 2010 2015 2020 Univ. of Tokyo Tokyo Metropolitan Geriatric Medical Center Univ. of Tokyo Novacor carried serious problems in Insurance Reimbursement Rule VAD? :1810305/ 31-904/6/ 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 VAD Novacor LVAD 0 Op (3m) 1y cost 2y cost 3y cost Cardiovascular Med-Surg 2005;7(2):279-283 (n=50), Novacor(n=5):
VAS() VAS () ( )() VAS VAS VAD (61) 1.0 0.8 0.6 0.4 VAD (Nipro VAD54 vs VAD: 20) 4 95 169 257 341 VAS(40) () 12,000,000 10,000,000 8,000,000 6,000,000 8 189/ (1511) VAS 3 1493 VAS 15 230/ (3448) 2 59/ (117) 4,000,000 2,000,000 3 878 0 06/3 06/11 08/5 0.2 0.0 0 365 730 1095 1460 () (8) 1511(189/) VAS(3) 1493 VAS(15) 3448(230/) (3) 878 (2) 117( 59/) 7447
() 1,000,000 800,000 600,000 400,000 200,000 0 (6) 1,400,000 605540/ 75444/ 68125/ 76393/ 1,200,000 05/9 06/3 06/9 07/3 07/9 08/3 08/9 712 605540/ 1324 75444/ 2536 68125/ 3742 76393/ () (-) (-) :(200420113) SpO 2 PT-INR
24 7000 6000 5000 4000 3000 2000 (2010) Novacor(2010) DuraHeart(2011) DuraHeart(2012) 1000 0 3 1 2 3 VAD2+ (K603-1,2,3,) DuraHeart+(K604-1,2,3,4) EVAHEARTDuraHeart(100) LVAD(24) LVAD : () BTT :60 DT
23811 5(2012.5.25) () ()