Lung Transplantation For Pediatric Pulmonary Hypertension No - - PowerPoint PPT Presentation

▶
lung transplantation for pediatric pulmonary hypertension
SMART_READER_LITE
LIVE PREVIEW

Lung Transplantation For Pediatric Pulmonary Hypertension No - - PowerPoint PPT Presentation

Nov 04, 2023 269 likes •354 views

4/20/2018 Conflicts & Disclosures Lung Transplantation For Pediatric Pulmonary Hypertension No conflicts of interests No relevant disclosures Funding Don Hayes, Jr., MD, MS, MEd Nationwide Childrens Hospital Cystic

slide-1
SLIDE 1

4/20/2018 1

Lung Transplantation For Pediatric Pulmonary Hypertension

Don Hayes, Jr., MD, MS, MEd Nationwide Children’s Hospital The Ohio State University Columbus, OH

Conflicts & Disclosures

  • No conflicts of interests
  • No relevant disclosures
  • Funding

– Cystic Fibrosis (CF) Foundation – National Institutes of Health – The CHEST Foundation – Ohio Solid Organ Transplant Consortium

Objectives

  • Review published criteria for lung transplantation

(LTx) referral/listing for pulmonary hypertension (PH)

  • Explore recent trends for LTx in children with PH
  • Examine challenges & parental/family concerns

associated with LTx for PH

  • Discuss clinical outcomes & factors influencing

mortality in pediatric PH before & after LTx

Pediatric Lung Transplant Centers

Boston Children’s Hospital

*

Children’s Hospital

  • f Philadelphia

Children’s Hospital

  • f Pittsburgh

Nationwide Children’s Hospital

* *

*

* * *

Lucile Packard Children's Hospital

  • St. Louis Children’s

Hospital Texas Children’s Hospital Cincinnati Children’s Hospital Medical Center

*

slide-2
SLIDE 2

4/20/2018 2

Pediatric Lung Transplants Indications by Age Group (1/00- 6/16)

Diagnosis < 1 1-5 6-10 11-17 Cystic Fibrosis 4 3.7% 116 50.0% 814 66.7% Non CF-bronchiectasis 2 0.9% 23 1.9% ILD 5 8.3% 9 8.3% 6 2.6% 37 3.0% ILD Other Specify Cause 6 10.0% 10 9.3% 21 9.1% 46 3.8% Pulmonary Hypertension/Pulmonary Arterial Hypertension 7 11.7% 28 25.9% 24 10.3% 100 8.2% PH Eisenmenger’s Syndrome 1 0.9% 2 0.9% 6 0.5% PHT Other 15 25.0% 21 19.4% 8 3.4% 20 1.6% Obliterative Bronchiolitis (non-Retransplant) 10 9.3% 26 11.2% 58 4.8% Bronchopulmonary Dysplasia 4 6.7% 4 3.7% 3 1.3% 3 0.2% ABCA3 Transporter Mutation 5 8.3% 4 3.7% 1 0.4% 1 0.1% Surfactant Protein B Deficiency 13 21.7% 4 3.7% 1 0.4% Surfactant Protein C Deficiency 1 0.9% 1 0.1% Retransplant (Obliterative Bronchiolitis) 4 3.7% 8 3.4% 41 3.4% Retransplant (not Obliterative Bronchiolitis) 4 3.7% 6 2.6% 41 3.4% COPD, with or without A1ATD 2 3.3% 1 0.9% 3 1.3% 10 0.8% Other 3 5.0% 3 2.8% 5 2.2% 20 1.6%

JHLT 2017; 36(10): 1037-1079

Pediatric Lung Transplants Indications by Year (Number)

20 40 60 80 100 120 140 160

Number of Transplants Transplant Year

CF ILD ILD Other OB (non-Retx) PHT Other PH/PAH Other

JHLT 2017; 36(10): 1037-1079

Pediatric Lung Transplants Age Distribution by Diagnosis (1/08-6/16)

0% 20% 40% 60% 80% 100% CF ILD ILD Other OB (non-Retx) PHT Other PH/PAH Other

% of Transplants

<1 1-5 6-10 11-17

JHLT 2017; 36(10): 1037-1079

slide-3
SLIDE 3

4/20/2018 3

Pediatric Lung Transplants Diagnosis Distribution by Era (1/88-6/16)

0% 20% 40% 60% 80% 100% 1988-1999 (N=634) 2000-2007 (N=679) 2008-6/2016 (N=942)

% of Transplants

CF ILD ILD Other OB (non-Retx) PH/PAH PHT Other Other

JHLT 2017; 36(10): 1037-1079

Published Criteria for LTx Referral

  • WHO Class III or IV symptoms

– During escalating therapy

  • Rapidly progressive disease

– Assuming no weight & rehabilitation concerns

  • Use of parenteral targeted PH therapy

– Regardless of symptoms or WHO Class

  • Known or suspected

– Pulmonary veno-occlusive disease (PVOD) – Pulmonary capillary hemangiomatosis

Weill D et al. JHLT 2015;34:1-15

Published Criteria for LTx Listing

  • WHO Class III or IV

– 3 mo trial of combo therapy, including prostanoids

  • Cardiac index < 2 L/min/m2
  • Mean right atrial pressure > 15 mmHg
  • 6-min walk test < 350 m
  • Clinical deterioration

– Significant hemoptysis – Pericardial effusion – Progressive right heart failure

  • Renal insufficiency
  • ↑ bilirubin, brain natriuretic peptide
  • Recurrent ascites

Weill D et al. JHLT 2015;34:1-15

Challenges of Pediatric PH for LTx

  • Heterogeneous population
  • Effect of therapeutic options

– Prostanoids – Endothelin receptor antagonists – Phosphodiesterase inhibitors

  • Wide referral/listing patterns

– Variations at respective centers

  • With rapid deterioration

– LTx bridging strategies are an option but more difficult

slide-4
SLIDE 4

4/20/2018 4

Parental/Family Concerns

  • Insight provided by parents

– Low success rate – High rejection rate – High post-LTx mortality – Not a cure – Potential need for another LTx – Buying time & not quality of life – Poor quality of life

  • Anti-rejection meds, Prolonged care, Hospital stays

– Other complications

  • Diabetes, Cancer

From George Mallory, MD

Underappreciated Factors

  • Far fewer & more distant LTx centers

– Referral, evaluation, & relocation for listing is

  • nerous
  • Higher mortality on waitlist
  • Younger age donors

– Lungs most compromised of transplantable organs

  • Higher priority for 1A & 1B heart candidates

when heart-lungs being considered

– Most PH candidates listed for heart-lung are status 2 on heart list – Heart pulls the lungs but not vice versa

Prognosis of Pediatric PH

  • Spanish Registry Study

– 225 patients, 21 centers – Epidemiology/outcomes & phenotypical characterization of pediatric PH – First registry reporting moderate to severe PH in children using Nice groups II, III, IV, & V

del Cerro Marín MJ et al. AJRCCM 2014;190:1421-9

Spanish Study Pediatric PH Cohort

del Cerro Marín MJ et al. AJRCCM 2014;190:1421-9

Pulmonary arterial hypertension (PAH)

slide-5
SLIDE 5

4/20/2018 5

Prognosis of Pediatric PH

  • Mean age at diagnosis 4.3 ± 4.9 yrs

– 50% < 2 yrs of age

  • Survival rates (whole cohort – pulmonary

vascular disease)

– 1-yr: 80% – 3-yr: 74%

  • Survival rates (PAH cohort)

– 1-yr: 89% – 3-yr: 85%

del Cerro Marín MJ et al. AJRCCM 2014;190:1421-9

Survival by “Nice Etiologic” Group

del Cerro Marín MJ et al. AJRCCM 2014;190:1421-9

Survival by (A) Functional Class (FC) at Diagnosis & (B) Age at Diagnosis

del Cerro Marín MJ et al. AJRCCM 2014;190:1421-9

Mortality & Children with PH

  • Risk factors for mortality

– Etiologic group other than PAH – Age at diagnosis < 2 yrs – Advanced functional class at diagnosis – Elevated right atrial pressure at diagnosis

del Cerro Marín MJ et al. AJRCCM 2014;190:1421-9

slide-6
SLIDE 6

4/20/2018 6

Post-Transplant Outcomes: Pediatric PH

  • Published work: cohorts of 5-23 patients1-3

– Severely limiting the ability to predict post- transplant outcomes – 1-yr survival rates: range from 87-100% – Schaellibaum et al: 3-yr survival estimates of 84% – Goldstein et al: 5-yr survival of 61%

1Lammers AE et al. Pediatr Pulmonol 2010;45:263-9 2Schaellibaum G et al. Pediatr Pulmonol 2011;46:1121-7 3Goldstein BS et al. JHLT 2011;30:1148-52

Pediatric PH Referred for LTx

Lammers AE et al. Pediatr Pulmonol 2010;45:263-9

.

Pediatric PH Listed for LTx

Goldstein BS et al. JHLT 2011;30:1148-52

UNOS Registry Analysis

  • United Network for Organ Sharing Registry

– May 2005 to Dec 2015, F/U data through Dec 2016

  • Analysis

– Patient survival: Kaplan-Meier (KM) curves, log-rank tests, & univariate Cox proportional hazards regression

  • Results

– 156 children < 18 yrs of age listed for LTx or HLTx for PPH

  • 29 died on waitlist

– 65 children (26/39 boys/girls, age 10 ± 6 yrs)

  • 47 bilateral LTx; 18 combined heart-lung transplantation (HLTx)
  • Deaths after transplant

– 19 in LTx cohort; 9 in HLTx cohort – KM curve: 5-year survival rates » 61% for LTx » 48% for HLTx Unpublished Data

slide-7
SLIDE 7

4/20/2018 7

KM Curve: Post-Transplant for PPH Age < 18 yrs compared to other indications, 5/05-12/15

Unpublished Data

0.00 0.20 0.40 0.60 0.80 1.00

Proportion surviving

1 2 3 4 5 6 7 8 9 10

Time after transplant (years)

LTx for PPH HLTx for PPH LTx for other indications HLTx for other indications

Univariate Cox Regression

Unpublished Data Mean (SD)

  • r N (%)

HR (95% CI) P Age (y) 10 (6) 0.93 (0.88, 0.995) 0.036 Female 39 (60%) 1.47 (0.68, 3.21) 0.329 Calculated LAS (35 patients) 34 (4) 1.04 (0.92, 1.17) 0.555 Status 1A (18 patients) 15 (83%) 0.77 (0.20, 2.90) 0.700 Mean PAP (mmHg) (36 patients) 73 (21) 0.99 (0.97, 1.01) 0.282

Conclusions

  • Children with PH should be considered for LTx
  • Early referral is absolutely OK!
  • Referral for transplantation

– At diagnosis in non-PAH pulmonary vascular diseases – Poor functional class

  • WHO Class II with poor clinical trajectory
  • WHO Class III or IV

– Elevated right atrial pressure

  • Clinical scenarios to consider referral
  • Hemoptysis, Declining cardiac function
  • Escalating therapy, Need for parenteral therapy
  • No reduction in PVRI with vasodilator testing
  • PVOD, pulmonary capillary hemangiomatosis, alveolar

capillary dysplasia with misalignment of pulmonary veins