Pediatric Cardiac Transplantation Present and Future Jeffrey - - PDF document

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Pediatric Cardiac Transplantation Present and Future Jeffrey - - PDF document

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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

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9/4/2018 1

Pediatric Cardiac Transplantation Present and Future

Jeffrey Gossett, M.D., F.A.A.P. Director Heart Failure, Heart Transplantation Benioff Children’s Hospitals

Disclosure

  • I have no relevant financial relationships with any companies

related to the content of this course.

Objectives

  • To provide an overview of pediatric cardiac transplantation
  • What is the pediatric population that requires a OHT?
  • 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

Objectives

  • To provide an overview of pediatric cardiac transplantation
  • What is the pediatric population that requires a OHT?
  • How do they do?
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A nod to history

  • First cardiac transplant:
  • 12/3/1967: Christiaan Barnard - Cape Town
  • First infant cardiac transplant
  • 12/6/1967: Adrian Kantrowitz – Brooklyn

‒ No immunosuppression

  • 1984 Loma Linda – Baby Fae
  • Managed with CSA – died POD #20
  • First successful Neonatal Transplant: November 15, 1985
  • Leonard L. Bailey – Loma Linda, California
  • Still alive as of 11/17

So where have we come to?

ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079

100 200 300 400 500 600 700 Number of Transplants 11-17 6-10 1-5 <1

United States

United Network for Organ Sharing

< 1 year old 6 – 10 years old 11 – 18 years old

2009-6/2015 1988-2003

73% 21% 1% 4% 55% 38% 0.3% 7%

CHD DCM Retransplant Other

40% 47% 3% 9% 41% 44% 4% 11% 26% 58% 5% 11% 23% 54% 8% 15% 34% 44% 9% 13% 35% 44% 6% 15%

1 – 5 years old

Who gets a transplant?

ISHLT Annual Report 2016; JHLT 2016 Oct; 35(10) 1149-1205

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Patients Bridged with Mechanical Circulatory Support

22.1 21.3 22.5 22.4 29.4 25.4 26.3 29.7 34.8 32.9 10 20 30 40 50 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

% of Patients

ECMO VAD + ECMO VAD or TAH

ISHLT Annual Report 2016; JHLT 2016 Oct; 35(10) 1149-1205

Ventricular Assist Devices- Berlin Heart

  • Para-corporeal VAD
  • Pulsatile flow

‒ Adults think we’re nuts!

  • Complication profile is not great

‒ Neurologic concerns/strokes

  • But it’s what we got!

Pulsatile outcome (Berlin)

http://www.uab.edu/medicine/intermacs/images/Federal_Quarterly_Report/Statistical _Summaries/Pedimacs_-_Federal_Partners_Report_2017_Q1.pdf

  • 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!

Ventricular Assist Devices- Heartware

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Continuous flow outcomes

http://www.uab.edu/medicine/intermacs/images/Federal_Quarterly_Report/Statistical _Summaries/Pedimacs_-_Federal_Partners_Report_2017_Q1.pdf

Outcomes- GRAFT Survival 1982-2015

ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079

25 50 75 100 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

Survival (%) Years

<1 Year (N = 3,108) 1-5 Years (N = 2,934) 6-10 Years (N = 1,888) 11-17 Years (N = 5,065) Overall (N = 12,995)

Median survival (years): <1=22.3; 1-5=18.4; 6-10=14.4; 11-17=13.1

Outcomes– ERA effect

25 50 75 100 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

Survival (%) Years

1982-1989 (N=907) 1990-2003 (N=5,668) 2004-2008 (N=2,535) 2009-6/2015 (N=3,885) Median survival (years):1982-1989= 9.8; 1990-2003=14.4; 2004-2008=NA; 2009-6/2015=NA

ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079

Outcomes–2004-2015 conditional

ISHLT Annual Report 2017; JHLT 2017 Oct; 36(10) 1037-1079

50 60 70 80 90 100 1 2 3 4 5 6 7 8 9 10 11

Survival (%) Years

<1 Year (N = 1,168) 1-5 Years (N = 1,228) 6-10 Years (N = 791) 11-17 Years (N = 2,074) Overall (N = 5,261)

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Outcomes quality of life

0% 20% 40% 60% 80% 100%

1 Year (N = 2,134) 5 Year (N = 1,415) 10 Year (N = 554) No Activity Limitations Performs with Some Assistance Requires Total Assistance

J Heart Lung Transplant 2008;27: 937-983

Objectives

  • Describe the changing face of congenital transplantation
  • Shifting single ventricle population
  • Congenital Heart Disease
  • This population is changing
  • Shift from early mortality

JACC 2010 56(14):1149-57

Congenital Heart Patients

ATS 2012; 94:807-16

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1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) Cardiomyopathy 11/50 (22) 40/116 (34) 70/141 (49) CHD 37/50 (74) 69/116 (60) 67/141 (48) Single V (% of CHD) Without palliation 30/37 (81) 33/70 (47) 12/67 (18) After palliation 3/37 (8) 9/70 (13) 16/67 (24) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) Biventricular CHD 3/37 (8) 17/70 (24) 15/67 (22) Redo transplant 2/50 (4) 7/116 (6) 4/141 (3)

Congenital Heart Patients

  • Increasing incidence of cardiomyopathy??

ATS 2012; 94:807-16

1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) Cardiomyopathy 11/50 (22) 40/116 (34) 70/141 (49) CHD 37/50 (74) 69/116 (60) 67/141 (48) Single V (% of CHD) Without palliation 30/37 (81) 33/70 (47) 12/67 (18) After palliation 3/37 (8) 9/70 (13) 16/67 (24) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) Biventricular CHD 3/37 (8) 17/70 (24) 15/67 (22) Redo transplant 2/50 (4) 7/116 (6) 4/141 (3) 1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) Cardiomyopathy 11/50 (22) 40/116 (34) 70/141 (49) CHD 37/50 (74) 69/116 (60) 67/141 (48) Single V (% of CHD) Without palliation 30/37 (81) 33/70 (47) 12/67 (18) After palliation 3/37 (8) 9/70 (13) 16/67 (24) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) Biventricular CHD 3/37 (8) 17/70 (24) 15/67 (22) Redo transplant 2/50 (4) 7/116 (6) 4/141 (3)

Congenital Heart Patients

  • Shift away from primary transplant for HLHS/single ventricle

‒ “Transplantation for heart failure related to failed SV palliation has become the most common indication for patients with CHD”

ATS 2012; 94:807-16

1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) Cardiomyopathy 11/50 (22) 40/116 (34) 70/141 (49) CHD 37/50 (74) 69/116 (60) 67/141 (48) Single V (% of CHD) Without palliation 30/37 (81) 33/70 (47) 12/67 (18) After palliation 3/37 (8) 9/70 (13) 16/67 (24) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) Biventricular CHD 3/37 (8) 17/70 (24) 15/67 (22) Redo transplant 2/50 (4) 7/116 (6) 4/141 (3)

Shifting Single Ventricles

  • 1986-93: 30/37 without palliation
  • 81 % of CHD and 60% of TOTAL transplant volume!

1986-1993 n=22 (%) 1994-2001 n=90 (%) 2002-2009 n=141 (%) Cardiomyopathy 50 44 49 CHD 41 48 48 Single V (% of CHD) Without palliation 22 16 18 After palliation 33 21 24 After failed Fontan 11 21 34 Biventricular CHD 33 40 22 1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) Cardiomyopathy 22 34 49 CHD 74 60 48 Single V (% of CHD) Without palliation 81 47 18 After palliation 8 13 24 After failed Fontan 3 13 34 Biventricular CHD 8 24 22

  • So what happens if we take OUT most of those early HLHS?

1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) THE FUTURE?? N=171 (%) Cardiomyopathy 11/50 (22) 40/116 (34) 70/141 (49) 70/171 (40) CHD 37/50 (74) 69/116 (60) 67/141 (48) 95/171 (56) Single V (% of CHD) Without palliation 30/37 (81) 33/70 (47) 12/67 (18) 12/95 (13) After palliation 3/37 (8) 9/70 (13) 16/67 (24) 16/95 (17) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) 51/95 (54) Biventricular CHD 3/37 (8) 17/70 (24) 15/67 (22) 15/95 (16)

Future of OHT???

  • If we add most of the neonatal palliations back later

1986-1993 n=50 (%) 1994-2001 n=116 (%) 2002-2009 n=141 (%) THE FUTURE?? N=171 (%) Cardiomyopathy 11/50 (22) 40/116 (34) 70/141 (49) 70/171 (40) CHD 37/50 (74) 69/116 (60) 67/141 (48) 95/171 (56) Single V (% of CHD) Without palliation 30/37 (81) 33/70 (47) 12/67 (18) 12/95 (13) After palliation 3/37 (8) 9/70 (13) 16/67 (24) 16/95 (17) After failed Fontan 1/37 (3) 9/70 (13) 23/67 (34) 51/95 (54) Biventricular CHD 3/37 (8) 17/70 (24) 15/67 (22) 15/95 (16)

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Future of OHT??

  • Just focusing on the single ventricles then:

Present of OHT! Objectives

  • Discuss challenges of transplantation for failing Fontans
  • Plastic bronchitis/ Protein losing enteropathy
  • Early phase graft loss

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
  • Protein losing enteropathy (PLE)
  • Plastic Bronchitis (PB)
  • They just DON’T fit a box in UNet!
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Survival after OHT for Failed Fontan

  • What do they look like?
  • Multiple prior operations
  • Elevated Panel Reactive Antibody (PRA)
  • Poor nutritional status
  • Multi-organ system dysfunction typical

Typical point when we meet them! OHT for Failed Fontan: Lurie Children’s

  • 224 Transplants: 1988 – 2013
  • 23 failed Fontan
  • Mean age: 14.9 years (4.4 – 47 years)
  • Mean interval since Fontan 8.3 years
  • Mean # Prior operations = 3.7
  • PLE (n = 15)
  • Plastic Bronchitis (n = 2)
  • s/p Fontan Conversion (n = 8)
  • Ventilator (n = 8)

Ann Thorac Surg 2013; 96:1413-9 Ann Thorac Surg 2013; 96:1413-9

Results

  • 5 early deaths (23%)
  • No clear risk factors (likely due to n)
  • Renal failure a concern
  • PLE resolved in all survivors
  • Plastic Bronchitis resolved in all survivors
  • Pulmonary AVMs resolved as well
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Protein Losing Enteropathy

  • Protein loss through from the GI tract
  • In CHD dominantly reported in single ventricle pts after Fontan
  • Etiology unclear
  • ? increased hydrostatic pressure
  • Non-pulsatile flow?
  • Altered cardiac output
  • Seen despite “optimal” Fontan hemodynamics
  • With preserved and decreased function
  • Many potential treatments described
  • Historically significant mortality/morbidity

PHTS PLE Project

  • Compared transplantation after Fontan with vs without PLE
  • 96 patients with PLE vs 260 without
  • Patients with PLE were:

‒ Older (12.2 vs 8.7yrs) ‒ Larger (BSA 1.1 vs 0.9m2) ‒ Lower serum Bili (0.5 vs. 0.9mg/dl) ‒ Lower BNP (59 vs 227pg/ml) ‒ Lower Albumin (2.7 vs 3.8 gm/dl) ‒ Lower PCW (10.5 vs 14mmHg) ‒ Less PB (9.1 vs 26.1%) ‒ Less intubation (3.1 vs 13.1%)

Schumacher, Gossett et al J Heart Lung Tx 2015; 34:1169-76

PHTS PLE Project

Schumacher, Gossett et al J Heart Lung Tx 2015; 34:1169-76

Plastic Bronchitis

  • Formation of occlusive airway casts
  • In CHD dominantly reported in single ventricle pts after Fontan
  • Etiology/treatment unclear
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PHTS Plastic Bronchitis project

  • Multicenter prospective database in pediatric OHT
  • Captures ~85% of peds OHT
  • 10/35 centers had patients with PB
  • 14 TOTAL patients
  • 10 patients underwent OHT
  • Early mortality was higher
  • Conditional (after 30 d) and late (to 5 year) survival was

equivalent

  • Plastic Bronchitis resolved in ALL survivors
  • Same shown repeatedly for PLE

Gossett et al. JACC 2013;61:985-986

PHTS Plastic Bronchitis project

Gossett et al. JACC 2013;61:985-986

Survival after OHT for Failed Fontan

Bernstein et al Circ 2006; 114:273-80

Current Era

Simpson et al ATS 2017; 103:1315-21

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ACHD vs non-CHD

Bryant and Morales Ann Cardiothorac Surg 2018;7(1):143-151 based on Doumouras et al J Heart Lung Transplant 2016;35:1337–1347

Supporting the SV to OHT

  • All of our outcomes are hurt by early phase mortality
  • Earlier referral

‒ Better listing concepts/criteria

  • Better prediction and prevention of comorbidities
  • Better options for reversing end organ injury through support?

Supporting the SV to OHT

  • VAD support for the SV
  • Very limited numbers

‒ ~15-20% of Pedimacs implants for SV overall * ‒ ~5% for Fontan *

  • Devices applied:

‒ Heartware (systemic); TAH; Jarvik VAD (FTN); Berlin (FTN, systemic); Heartmate; Tandem (systemic) ‒ Certainly others!

  • Mortality and morbidity too high– We MUST do better!

* Pedimacs unpublished communications

Conclusions

  • World wide OHT numbers are relatively static
  • Organ availability must increase
  • Longer waiting times mitigated by improved medical therapies
  • VAD therapies in pediatrics lag far behind adult counterparts
  • More congenital patients will be coming!
  • Higher up front mortality, but better long term!
  • Single ventricle patients are challenging, but will be the future
  • We must find better support options to maximize outcomes
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Remind me why we do this???

http://www.nytimes.com/2009/08/12/us/12huesman.html?_r=1&ref=health

Thank you!

  • Jeffrey.Gossett@UCSF.edu

(773) 612-4104