Whats New Since Nice 2013 Whats New Since Nice 2013 in Pediatric - PowerPoint PPT Presentation

4/21/2018 WSPH 2018: Task Force 12 TASK FORCE 12 Pediatric Pulmonary Hypertension Pediatrics ERIKA ROSENZWEIG MD, Chair New York , NY USA ROLF M. F. BERGER MD, Chair Groningen, THE NETHERLANDS STEVEN ABMAN, MD Aurora, CO USA IAN ADATIA, MD Edmonton, CANADA MAURICE BEGHETTI, MD Geneve, SWITZERLAND DAMIEN BONNET, MD Paris, FRANCE CHRISTINE GARNETT, PD Silver Spring, MD USA SHEILA HAWORTH , MD London, UK DUNBAR IVY, MD Aurora, CO USA What’s New Since Nice 2013 What’s New Since Nice 2013 in Pediatric PH? in Pediatric PH? 2017 Circulation. 2015;132:2037-2099 Heart 2016;102:ii86-ii100. 1

4/21/2018 What’s New Since Nice 2013 Pediatric Patient Registries have in Pediatric PH? been established and growing • Expansion of PAH drug approval in children in US (n=1)! • PPHnet (North America) ~1500 patients • TOPP 1 and 2 registry (International) ~800 • Expansion of use of interventional-surgical approaches for end-stage PAH • Spanish registry ~225 in children • German registry ~200 • REVEAL pediatric ~200 • Genetic discoveries relevant to pediatric practice Total ~3000 • New insights from pediatric specific registry data Pediatric Definitions: Update? Task Force PH/PAH definition considerations PH = PAPm > 25mmHg was the same in children and adults PRO CON PAH = PAPm > 25mmHg with PAWPm < 15mmHg was the same • Not sufficient data on PAPm of • Common language 21-24mmHg in children or sub- groups We discussed alignment with the adult definition: • Younger children with lower • PAPm >25mmHg change to > 20mmHg resting SBP may be included • Pediatric registries have not used • Add PVRi > 3 U*m2 this definition • Borderline children under • More useful to use a ratio of anesthesia at time of RHC may Adding “in children over 3 months of age” PAP/SAP in young children = be included >0.5 because SAP varies with age • Includes PVRi (CHD) Task force debated over this change in pediatric definition 2

4/21/2018 New proposed Heritable PAH pediatric PH and PAH definitions • Known mutations: BMPR2, ALK1, ENG, CAV1, KCNK3, EIF2AK4 • TBX4 – described potential role in pediatric PAH and small patella PH = PAPm > 20mmHg and PVRi > 3U*m2 syndrome, (Kerstjens-Frederikse WS, 2013) PAH = PAPm > 20mmHg and PAWPm <15mmHg and • In one French Study – ACVRL 1 and TBX4 more common in children PVRi >3 U*m2 than adults, (Levy M, ERJ, 2016) • Similar experience in US Cohort, (Zhu Circ Genom Precis Med. 2018;11) ...in children over 3 months of age • SOX 17 : transcription factor - ?CHD Updated clinical classification (Nice 2018) Comparison of Genetic Test Results in Adults and Children 1. Pulmonary Arterial Hypertension 3. PH due to lung diseases and/or hypoxia 1.1 Idiopathic PAH Adult Pediatric (age < 18) 3.1 Chronic obstructive Lung Diseases 1.2 PAH with long-term response to Ca blockers 1.3 Heritable PAH (Table 1) 3.2 Interstitial Lung Diseases 3.3 Other LD with restrictive/obstructive pattern 1.4 Drugs and Toxins induced (Table 2) 3.4 Hypoxia without lung diseases 1.5 Associated with; 3.5 Developmental Lung Disorders (Table P3) 1.4.1 Connective tissue disease (Table 3) 1.5.2 HIV infection FPAH 4. PH due to pulmonary artery obstruction 1.5.3 Portal hypertension 1.5.4 Congenital heart diseases (Table 4) 4.1 Chronic Thromboembolic PH N=79 1..5 Schistosomiasis N=25 4.2 Other Pulmonary artery obstructions (Table 7) 1.6 PAH with overt signs of venous/capillaries ( PVOD/PCH) involvement (Table 5 & 6) 1.7 PPHN Syndrome (Table P1) 5. PH with unclear mechanisms IPAH 2. PH due to left heart disease 5.1 Haematologic disorders (Table 8) 2.1 PH due to Heart Failure with preserved E.F. 5.2 Systemic disorders ( Table 8) 2.2 PH due to Heart Failure with reduced E.F. 5.3 Others 2.3 Valvular Disease Courtesy of Dr. Wendy Chung N=178 N=130 5.4 Complex CHD (Table P4) 2.4 Congenital Post-Capillary Obstruction (Table P2) 3

4/21/2018 Updated clinical classification (Nice 2018) Table 4. Proposed Clinical Classification of PAH Associated with CHD 1. Pulmonary Arterial Hypertension 3. PH due to lung diseases and/or hypoxia 1.1 Idiopathic PAH 3.1 Chronic obstructive Lung Diseases 1.2 PAH with long-term response to Ca blockers A. Eisenmenger Syndrome 3.2 Interstitial Lung Diseases 1.3 Heritable PAH (Table 1) 3.3 Other LD with restrictive/obstructive pattern 1.4 Drugs and Toxins induced (Table 2) 1.5 Associated with; 3.4 Hypoxia without lung diseases B. Left to Right Shunts 3.5 Developmental Lung Disorders (Table P3) 1.4.1 Connective tissue disease (Table 3) - Non-correctable 1.5.2 HIV infection - Correctable 4. PH due to pulmonary artery obstruction 1.5.3 Portal hypertension 1.5.4 Congenital heart diseases (Table 4) 4.1 Chronic Thromboembolic PH C. PAH with co-incidental CHD 1..5 Schistosomiasis 4.2 Other Pulmonary artery obstructions (Table 7) 1.6 PAH with overt signs of venous/capillaries ( PVOD/PCH) involvement (Table 5 & 6) D. Post-operative PAH 1.7 PPHN Syndrome (Table P1) 5. PH with unclear mechanisms 2. PH due to left heart disease 5.1 Haematologic disorders (Table 8) 2.1 PH due to Heart Failure with preserved E.F. Previous definition of PAH based on mean PAP > 25mmHg; 5.2 Systemic disorders ( Table 8) 2.2 PH due to Heart Failure with reduced E.F. PVR provides essential information for CHD patients 5.3 Others 2.3 Valvular Disease 5.4 Complex CHD (Table P4) 2.4 Congenital Post-Capillary Obstruction (Table P2) Updated clinical classification (Nice 2018) Table P1. PPHN Syndrome - Associated Conditions 1. Pulmonary Arterial Hypertension 3. PH due to lung diseases and/or hypoxia 1.1 Idiopathic PAH 3.1 Chronic obstructive Lung Diseases 1.2 PAH with long-term response to Ca blockers 1.3 Heritable PAH (Table 1) 3.2 Interstitial Lung Diseases 3.3 Other LD with restrictive/obstructive pattern 1.4 Drugs and Toxins induced (Table 2) Idiopathic PPHN Myocardial dysfunction (asphyxia, infection) 3.4 Hypoxia without lung diseases 1.5 Associated with; Structural cardiac diseases: Down syndrome 3.5 Developmental Lung Disorders (Table P3) 1.4.1 Connective tissue disease (Table 3) Hepatic and Cerebral arteriovenous malformations (AVMs) Meconium aspiration syndrome 1.5.2 HIV infection 4. PH due to pulmonary artery obstruction 1.5.3 Portal hypertension Respiratory distress syndrome Associations with other diseases 1.5.4 Congenital heart diseases (Table 4) Placental dysfunction (PE, chorioamnionitis, maternal htn) Transient tachypnea of the newborn 4.1 Chronic Thromboembolic PH 1..5 Schistosomiasis Metabolic disease 4.2 Other Pulmonary artery obstructions (Table 7) Pneumonia/sepsis 1.6 PAH with overt signs of venous/capillaries Maternal drug use or smoking ( PVOD/PCH) involvement (Table 5 & 6) Developmental lung disease (DLD) 1.7 PPHN Syndrome (Table P1) Perinatal stress 5. PH with unclear mechanisms 2. PH due to left heart disease 5.1 Haematologic disorders (Table 8) 2.1 PH due to Heart Failure with preserved E.F. 5.2 Systemic disorders ( Table 8) 2.2 PH due to Heart Failure with reduced E.F. 5.3 Others 2.3 Valvular Disease 5.4 Complex CHD (Table P4) 2.4 Congenital Post-Capillary Obstruction (Table P2) 4