4/21/2018 Disclaimer Pediatric Risk Stratification Models in - - PowerPoint PPT Presentation

▶
4 21 2018
SMART_READER_LITE
LIVE PREVIEW

4/21/2018 Disclaimer Pediatric Risk Stratification Models in - - PowerPoint PPT Presentation

Oct 21, 2022 168 likes •258 views

4/21/2018 Disclaimer Pediatric Risk Stratification Models in Children No conflicts of interest with Pulmonary Arterial Hypertension Marlies Haarman, MD Network Pediatric Pulmonary Hypertension University Medical Center Groningen - Center

slide-1
SLIDE 1

4/21/2018 1

Pediatric Risk Stratification Models in Children with Pulmonary Arterial Hypertension

Marlies Haarman, MD

Network Pediatric Pulmonary Hypertension

University Medical Center Groningen - Center for Congenital Heart diseases

Disclaimer

University Medical Center Groningen Center for Congenital Heart diseases

No conflicts of interest

Background

University Medical Center Groningen Center for Congenital Heart diseases

Time years Transplant-free survival %

1 2 3 4 5 20 40 60 80 100

  • Poor prognosis of patients with

pulmonary arterial hypertension (PAH)

  • A high need for improvement of

prognosis and refinement of treatment strategies

  • Risk stratification as a crucial

cornerstone in the standard care

  • f patients with PAH

Risk assessment in adult PAH

University Medical Center Groningen Center for Congenital Heart diseases

Galié et al., Eur Heart J, 2015.

slide-2
SLIDE 2

4/21/2018 2

Survival in adult PAH based on risk stratification

University Medical Center Groningen Center for Congenital Heart diseases

Boucly et al., Eur Respir J, 2017.

Survival in adult PAH based on risk stratification

University Medical Center Groningen Center for Congenital Heart diseases

Boucly et al., Eur Respir J, 2017.

Survival in adult PAH based on risk stratification

University Medical Center Groningen Center for Congenital Heart diseases

Boucly et al., Eur Respir J, 2017.

Pediatric determinants of risk

University Medical Center Groningen Center for Congenital Heart diseases

5th WSPH, Pediatric Task Force, JACC, 2013.

slide-3
SLIDE 3

4/21/2018 3

Pediatric determinants of risk

University Medical Center Groningen Center for Congenital Heart diseases

5th WSPH, Pediatric Task Force, JACC, 2013.

Pediatric determinants of risk Low-risk criteria

University Medical Center Groningen Center for Congenital Heart diseases

Determinants of risk Low-risk criterion WHO functional class I+II Syncope N0 Growth

  • Z-score BMI >-2
  • Z-score height >-2

NT-proBNP ≤1200 ng/L Echocardiography

  • TAPSE: ≥12mm
  • RA area: <18cm²

Hemodynamics

  • Acute vasoreactivity
  • Systemic CI ≥2.5 l/min/m2
  • mPAP/mSAP ≤0.75
  • RAP ≤10 mmHg
  • PVRi ≤20 WU*m2
  • SvO2 > 65%

6MWD ≥7years >352 m

Galié et al., Eur Heart J, 2015. 5th WSPH, Pediatric Task Force, JACC, 2013.

University Medical Center Groningen Center for Congenital Heart diseases

Determinants of risk Low-risk criterion WHO functional class I+II Syncope N0 Growth

  • Z-score BMI >-2
  • Z-score height >-2

NT-proBNP ≤1200 ng/L Echocardiography

  • TAPSE: ≥12mm
  • RA area: <18cm²

Hemodynamics

  • Acute vasoreactivity
  • Systemic CI ≥2.5 l/min/m2
  • mPAP/mSAP ≤0.75
  • RAP ≤10 mmHg
  • PVRi ≤20 WU*m2
  • SvO2 > 65%

6MWD ≥7years >352 m

Galié et al., Eur Heart J, 2015. 5th WSPH, Pediatric Task Force, JACC, 2013.

Pediatric determinants of risk Low-risk criteria Study design

University Medical Center Groningen Center for Congenital Heart diseases

  • Dutch national registry
  • Children ≤ 18 years with IPAH/HPAH
  • Pediatric WSPH risk model
  • Risk stratification:

– At diagnosis – At one-year follow-up

  • Outcome defined as transplant-free survival
  • Aim: to investigate the prognostic value of the pediatric WSPH risk model

at diagnosis and one-year follow-up

slide-4
SLIDE 4

4/21/2018 4

Models

University Medical Center Groningen Center for Congenital Heart diseases

  • 3 Models

– Model A: The full model – Model B: The model with non-invasive low-risk criteria

  • At diagnosis
  • At one-year follow-up

– Model C: The model with only those variables that were significantly associated with

  • utcome in univariable Cox regression analysis
  • At diagnosis
  • At one-year follow-up

Patient characteristics

University Medical Center Groningen Center for Congenital Heart diseases

Characteristics n(%), Median (IQR) Female 31 (53) Age at diagnosis, y 6.8 (2.2-13.4) Follow-up, y 3.1 (0.7-8.4) Mortality 24 (41) WHO-FC

  • I+II
  • III
  • IV

19 (33) 23 (40) 16 (27) NT-proBNP, ng/L 1391 (221-5911) 6MWD, m 382 (296-448)

Model A ‘The full model’

University Medical Center Groningen Center for Congenital Heart diseases

Model A ‘The full model’

University Medical Center Groningen Center for Congenital Heart diseases

Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 2 3 4 5 6 7 8 9 10 11 12

  • No. of

low-risk criteria

p=0.041

HR (95%CI) 0.78 (0.68-0.89) (p<0.001)

slide-5
SLIDE 5

4/21/2018 5

Univariable Cox regression analysis of low-risk criteria

University Medical Center Groningen Center for Congenital Heart diseases Low-risk criterion At diagnosis Hazard ratio (95% CI) p-value At 1-year follow-up Hazard ratio (95% CI) p-value WHO-FC I+II 0.21 (0.074-0.61) 0.004 0.29 (0.11-0.81) 0.018 No syncope 0.72 (0.33-1.55) 0.40 0.42 (0.10-1.68) 0.22 Z-score BMI > -2 0.73 (0.333-1.62) 0.44 2.05 (0.27-15.76) 0.49 Z-score height > -2 0.63 (0.26-1.53) 0.30 23.45 (0.003-159585) 0.48 TAPSE ≥ 12mm 0.57 (0.17-1.89) 0.35 1.00 (0.17-5.79) >0.999 RA area <18 cm² 0.78 (0.34-1.78) 0.56 0.66 (0.21-2.07) 0.47 NT-proBNP ≤1200 ng/L 0.37 (0.14-0.95) 0.038 0.31 (0.087-1.13) 0.075 mPAP/mSAP <0.75 0.51 (0.22-1.20) 0.12 NA

  • CI ≥2.5 l/min/m²

0.60 (0.28-1.31) 0.20 NA

  • mRAP ≤ 10 mmHg

0.43 (0.19-0.96) 0.040 NA

  • PVRi ≤20 WU∙m²

0.30 (0.13-0.71) 0.006 NA

  • SvO2, >65%

0.29 (0.12-0.69) 0.005 NA

  • 6MWD, >352 m

0.75 (0.59-0.94) 0.015 0.54 (0.19-1.51) 0.24

Univariable Cox regression analysis of low-risk criteria

University Medical Center Groningen Center for Congenital Heart diseases Low-risk criterion At diagnosis Hazard ratio (95% CI) p-value At 1-year follow-up Hazard ratio (95% CI) p-value WHO-FC I+II 0.21 (0.074-0.61) 0.004 0.29 (0.11-0.81) 0.018 No syncope 0.72 (0.33-1.55) 0.40 0.42 (0.10-1.68) 0.22 Z-score BMI > -2 0.73 (0.333-1.62) 0.44 2.05 (0.27-15.76) 0.49 Z-score height > -2 0.63 (0.26-1.53) 0.30 23.45 (0.003-159585) 0.48 TAPSE ≥ 12mm 0.57 (0.17-1.89) 0.35 1.00 (0.17-5.79) >0.999 RA area <18 cm² 0.78 (0.34-1.78) 0.56 0.66 (0.21-2.07) 0.47 NT-proBNP ≤1200 ng/L 0.37 (0.14-0.95) 0.038 0.31 (0.087-1.13) 0.075 mPAP/mSAP <0.75 0.51 (0.22-1.20) 0.12 NA

  • CI ≥2.5 l/min/m²

0.60 (0.28-1.31) 0.20 NA

  • mRAP ≤ 10 mmHg

0.43 (0.19-0.96) 0.040 NA

  • PVRi ≤20 WU∙m²

0.30 (0.13-0.71) 0.006 NA

  • SvO2, >65%

0.29 (0.12-0.69) 0.005 NA

  • 6MWD, >352 m

0.75 (0.59-0.94) 0.015 0.54 (0.19-1.51) 0.24

Model B ‘The non-invasive model’

University Medical Center Groningen Center for Congenital Heart diseases

Model B ‘The non-invasive model’

University Medical Center Groningen Center for Congenital Heart diseases

At diagnosis: HR (95%CI) 0.63 (0.49-0.82) (p=0.001)

Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 2 3 4 5 6 7

  • No. of

low-risk criteria

p=0.006

slide-6
SLIDE 6

4/21/2018 6

Model B ‘The non-invasive model’

University Medical Center Groningen Center for Congenital Heart diseases

At one-year follow-up: HR (95%CI) 0.61 (0.41-0.92) (p=0.019)

Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 2 3 4 5 6 7

  • No. of

low-risk criteria

p=0.006

Time (years) Transplant-free survival %

1 2 3 4 5 20 40 60 80 100 3 4 5 6 7

  • No. of

low-risk criteria

At diagnosis: HR (95%CI) 0.63 (0.49-0.82) (p=0.001)

Model C ‘The model with significant low-risk criteria’

University Medical Center Groningen Center for Congenital Heart diseases

Model C ‘The model with significant low-risk criteria’

University Medical Center Groningen Center for Congenital Heart diseases

At diagnosis: HR (95%CI) 0.64 (0.52-0.80) (p<0.001)

Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 1 2 3 4 5

  • No. of

low-risk criteria

p<0.001

Model C ‘The model with significant low-risk criteria’

University Medical Center Groningen Center for Congenital Heart diseases

At one-year follow-up: HR (95%CI) 0.30 (0.15-0.58)(p<0.001) At diagnosis: HR (95%CI) 0.64 (0.52-0.80) (p<0.001)

Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 1 2

  • No. of

low-risk criteria

Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 1 2 3 4 5

  • No. of

low-risk criteria

p<0.001

slide-7
SLIDE 7

4/21/2018 7

Treatment Algorithm

University Medical Center Groningen Center for Congenital Heart diseases

5th WSPH, Pediatric Task Force, JACC, 2013.

Treatment Algorithm

University Medical Center Groningen Center for Congenital Heart diseases

5th WSPH, Pediatric Task Force, JACC, 2013.

Treatment target

University Medical Center Groningen Center for Congenital Heart diseases

Treatment target

University Medical Center Groningen Center for Congenital Heart diseases Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 0-4 --> 0-4 0-4 --> 5-7 5-7 --> 5-7 5-7 --> 0-4

  • No. of low-risk criteria

at diagnosis --> no. of low-risk criteria at

  • ne-year follow-up

p=0.004

slide-8
SLIDE 8

4/21/2018 8

Treatment target

University Medical Center Groningen Center for Congenital Heart diseases Time (years) Transplant-free survival (%)

1 2 3 4 5 20 40 60 80 100 0-4 --> 0-4 0-4 --> 5-7 5-7 --> 5-7 5-7 --> 0-4

  • No. of low-risk criteria

at diagnosis --> no. of low-risk criteria at

  • ne-year follow-up

p=0.004

Time (years) Transplant-free survival %

1 2 3 4 5 20 40 60 80 100 0-1 --> 0-1 2 --> 0-1 2 --> 2 0-1 --> 2

  • No. of low-risk criteria

at diagnosis --> no. of low-risk criteria at

  • ne-year follow-up

p=0.04

Conclusions

University Medical Center Groningen Center for Congenital Heart diseases

  • The WSPH pediatric risk stratification model successfully predicts

transplant-free survival in pediatric PAH-patients, both at diagnosis and at one-year follow-up.

  • An abbreviated risk stratification model also accurately predicts

transplant-free survival.

  • Achieving a low-risk profile can be used as a treatment target.

Thank you for your attention

Department of Pediatric Cardiology, University Medical Center Groningen

University Medical Center Groningen Center for Congenital Heart diseases

  • S. Arjaans
  • R. Berger
  • G. Bossers
  • G. Eshuis
  • M. Douwes
  • D. vd Feen
  • A. Koop
  • Q. Hagdorn
  • L. Jorna
  • S. Meyer
  • F. Ridderbos

M-J. Ploegstra

  • R. van Loon
  • J. Vos
  • M. Fries
  • A. Wendt
  • D. vd Weerd
  • R. Visscher
  • A. Rackowitz
  • G. Du Marchie Sarvaas
  • M. Talsma
  • M. Roofthooft
  • W. Vanagt
  • N. Elzenga
  • F. vd Heuvel
  • E. Liem
  • H. Nijenhuis
  • T. Kazemier-Vissia
  • D. vd Weerd
  • R. Visscher
  • T. van Leusden
  • T. Willems
  • M. Veldhuizen
  • K. Kol
  • L. Stuifzand-de Bats
  • G. de Groot-Brinks

Network Pediatric Pulmonary Hypertension

Questions?

University Medical Center Groningen Center for Congenital Heart diseases

Network Pediatric Pulmonary Hypertension