Pediatric Cardiac Transplantation Present and Future Jeffrey - PDF document

Disclosure  I have no relevant financial relationships with any companies related to the content of this course. Pediatric Cardiac Transplantation Present and Future Jeffrey Gossett, M.D., F.A.A.P. Director Heart Failure, Heart Transplantation Benioff Children’s Hospitals Objectives Objectives  To provide an overview of pediatric cardiac transplantation  To provide an overview of pediatric cardiac transplantation • What is the pediatric population that requires a OHT? • What is the pediatric population that requires a OHT? • How do they do? • How do they do?  Describe the changing face of congenital transplantation  • Shifting single ventricle population •  Discuss challenges of transplantation for failing Fontans  • Plastic bronchitis/ Protein losing enteropathy • • Early phase graft loss • 1 9/4/2018

A nod to history So where have we come to? 700  First cardiac transplant: 11-17 600 • 12/3/1967: Christiaan Barnard - Cape Town 6-10 1-5 500  First infant cardiac transplant Number of Transplants <1 • 12/6/1967: Adrian Kantrowitz – Brooklyn 400 ‒ No immunosuppression 300  1984 Loma Linda – Baby Fae 200 • Managed with CSA – died POD #20  First successful Neonatal Transplant: November 15, 1985 100 • Leonard L. Bailey – Loma Linda, California 0 • Still alive as of 11/17 ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079 United States Who gets a transplant? 1988-2003 2009-6/2015 55% 73% < 1 year old 7% CHD 4% 1% 0.3% 38% 21% DCM 41% 40% 1 – 5 years old 11% Retransplant 9% 44% 3% 47% 4% Other 34% 35% 6 – 10 years old 15% 13% 44% 44% 9% 6% 26% 23% 11 – 18 years old 54% 58% 15% 11% 5% 8% United Network for Organ Sharing ISHLT Annual Report 2016; JHLT 2016 Oct; 35(10) 1149-1205 2 9/4/2018

Patients Bridged with Mechanical Ventricular Assist Devices- Berlin Heart Circulatory Support 50  Para-corporeal VAD ECMO VAD + ECMO VAD or TAH  Pulsatile flow 40 ‒ Adults think we’re nuts! 34.8 32.9 % of Patients 29.4 29.7  Complication profile is not great 30 26.3 25.4 22.5 22.4 22.1 ‒ Neurologic concerns/strokes 21.3 20  But it’s what we got! 10 0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 ISHLT Annual Report 2016; JHLT 2016 Oct; 35(10) 1149-1205 Pulsatile outcome (Berlin) Ventricular Assist Devices- Heartware  Intra-corporeal VAD • Continuous flow ‒ Standard of care for adults  Big two are Heartware (HVAD) and Heartmate II • Complication profile is dramatically better  But it’s gotta fit! • Almost for sure >40kg • Probably 20-40kg (been done down to ~15 kgs)  Discharge possible! http://www.uab.edu/medicine/intermacs/images/Federal_Quarterly_Report/Statistical _Summaries/Pedimacs_-_Federal_Partners_Report_2017_Q1.pdf 3 9/4/2018

Continuous flow outcomes Outcomes- GRAFT Survival 1982-2015 100 <1 Year (N = 3,108) 1-5 Years (N = 2,934) 6-10 Years (N = 1,888) 75 11-17 Years (N = 5,065) Overall (N = 12,995) Survival (%) 50 25 Median survival (years): <1=22.3; 1-5=18.4; 6-10=14.4; 11-17=13.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Years ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079 http://www.uab.edu/medicine/intermacs/images/Federal_Quarterly_Report/Statistical _Summaries/Pedimacs_-_Federal_Partners_Report_2017_Q1.pdf Outcomes– ERA effect Outcomes–2004-2015 conditional 100 100 1982-1989 (N=907) 1990-2003 (N=5,668) 2004-2008 (N=2,535) 2009-6/2015 (N=3,885) 90 75 Survival (%) Survival (%) 80 50 70 25 <1 Year (N = 1,168) 1-5 Years (N = 1,228) 60 Median survival (years):1982-1989= 9.8; 1990-2003=14.4; 6-10 Years (N = 791) 11-17 Years (N = 2,074) 2004-2008=NA; 2009-6/2015=NA Overall (N = 5,261) 0 50 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 0 1 2 3 4 5 6 7 8 9 10 11 Years Years ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079 ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079 4 9/4/2018

Outcomes quality of life Objectives  100% • 80% •  Describe the changing face of congenital transplantation 60% • Shifting single ventricle population 40%  • 20% • No Activity Limitations Performs with Some Assistance Requires Total Assistance 0% 1 Year (N = 2,134) 5 Year (N = 1,415) 10 Year (N = 554) J Heart Lung Transplant 2008;27: 937-983 Congenital Heart Disease Congenital Heart Patients  This population is changing • Shift from early mortality ATS 2012; 94:807-16 JACC 2010 56(14):1149-57 5 9/4/2018

Congenital Heart Patients Congenital Heart Patients 1986-1993 1986-1993 1994-2001 1994-2001 2002-2009 2002-2009 1986-1993 1986-1993 1994-2001 1994-2001 2002-2009 2002-2009 n=50 n=50 n=116 n=116 n=141 n=141 n=50 n=50 n=116 n=116 n=141 n=141 (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) Cardiomyopathy Cardiomyopathy 11/50 (22) 11/50 (22) 40/116 (34) 40/116 (34) 70/141 (49) 70/141 (49) Cardiomyopathy Cardiomyopathy 11/50 (22) 11/50 (22) 40/116 (34) 40/116 (34) 70/141 (49) 70/141 (49) CHD CHD 37/50 (74) 37/50 (74) 69/116 (60) 69/116 (60) 67/141 (48) 67/141 (48) CHD CHD 37/50 (74) 37/50 (74) 69/116 (60) 69/116 (60) 67/141 (48) 67/141 (48) Single V (% of CHD) Single V (% of CHD) Single V (% of CHD) Single V (% of CHD) Without palliation Without palliation 30/37 (81) 30/37 (81) 33/70 (47) 33/70 (47) 12/67 (18) 12/67 (18) After palliation After palliation 3/37 (8) 3/37 (8) 9/70 (13) 9/70 (13) 16/67 (24) 16/67 (24) Without palliation Without palliation 30/37 (81) 30/37 (81) 33/70 (47) 33/70 (47) 12/67 (18) 12/67 (18) After failed Fontan After failed Fontan 1/37 (3) 1/37 (3) 9/70 (13) 9/70 (13) 23/67 (34) 23/67 (34) After palliation After palliation 3/37 (8) 3/37 (8) 9/70 (13) 9/70 (13) 16/67 (24) 16/67 (24) Biventricular CHD Biventricular CHD 3/37 (8) 3/37 (8) 17/70 (24) 17/70 (24) 15/67 (22) 15/67 (22) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) Redo transplant Redo transplant 2/50 (4) 2/50 (4) 7/116 (6) 7/116 (6) 4/141 (3) 4/141 (3) Biventricular CHD Biventricular CHD 3/37 (8) 3/37 (8) 17/70 (24) 17/70 (24) 15/67 (22) 15/67 (22)  Shift away from primary transplant for HLHS/single ventricle Redo transplant Redo transplant 2/50 (4) 2/50 (4) 7/116 (6) 7/116 (6) 4/141 (3) 4/141 (3)  Increasing incidence of cardiomyopathy?? ‒ “Transplantation for heart failure related to failed SV palliation has become the most common indication for patients with CHD” ATS 2012; 94:807-16 ATS 2012; 94:807-16 Shifting Single Ventricles Future of OHT???  1986-93: 30/37 without palliation  If we add most of the neonatal palliations back later • 81 % of CHD and 60% of TOTAL transplant volume! 1986-1993 1986-1993 1994-2001 1994-2001 2002-2009 2002-2009 THE FUTURE?? THE FUTURE?? n=50 n=50 n=116 n=116 n=141 n=141 1986-1993 1994-2001 2002-2009 1986-1993 1994-2001 2002-2009 N=171 N=171 n=22 n=90 n=141 (%) (%) (%) (%) (%) (%) (%) (%) n=50 n=116 n=141 (%) (%) (%) (%) (%) (%) Cardiomyopathy Cardiomyopathy 11/50 (22) 11/50 (22) 40/116 (34) 40/116 (34) 70/141 (49) 70/141 (49) 70/171 (40) 70/171 (40) Cardiomyopathy 22 34 49 Cardiomyopathy 50 44 49 CHD 74 60 48 CHD 41 48 48 CHD CHD 37/50 (74) 37/50 (74) 69/116 (60) 69/116 (60) 67/141 (48) 67/141 (48) 95/171 (56) 95/171 (56) Single V (% of CHD) Single V (% of CHD) Single V (% of CHD) Single V (% of CHD) Without palliation 81 47 18 Without palliation 22 16 18 Without palliation Without palliation 30/37 (81) 30/37 (81) 33/70 (47) 33/70 (47) 12/67 (18) 12/67 (18) 12/95 (13) 12/95 (13) After palliation 33 21 24 After palliation 8 13 24 After failed Fontan 3 13 34 After failed Fontan 11 21 34 After palliation After palliation 3/37 (8) 3/37 (8) 9/70 (13) 9/70 (13) 16/67 (24) 16/67 (24) 16/95 (17) 16/95 (17) Biventricular CHD 8 24 22 Biventricular CHD 33 40 22 After failed Fontan After failed Fontan 1/37 (3) 1/37 (3) 9/70 (13) 9/70 (13) 23/67 (34) 23/67 (34) 51/95 (54) 51/95 (54) Biventricular CHD Biventricular CHD 3/37 (8) 3/37 (8) 17/70 (24) 17/70 (24) 15/67 (22) 15/67 (22) 15/95 (16) 15/95 (16) • So what happens if we take OUT most of those early HLHS? 6 9/4/2018

Future of OHT?? Present of OHT!  Just focusing on the single ventricles then: Objectives The “Failed Fontan”   Uni-ventricular heart with “heart failure” ‒ Different from “typical” adult heart failure •  Ventricular dysfunction (or NOT) •  AV valve regurg   Arrhythmia •  Hepatic insufficiency  Discuss challenges of transplantation for failing Fontans  Protein losing enteropathy (PLE) • Plastic bronchitis/ Protein losing enteropathy  Plastic Bronchitis (PB) • Early phase graft loss • They just DON’T fit a box in UNet! 7 9/4/2018